{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:22:53Z","timestamp":1788996173500,"version":"build-2803163510"},"reference-count":169,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T00:00:00Z","timestamp":1677542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Life Sciences, UNIMORE","award":["19786"],"award-info":[{"award-number":["19786"]}]},{"name":"Department of Life Sciences, UNIMORE","award":["813863"],"award-info":[{"award-number":["813863"]}]},{"name":"AIRC","award":["19786"],"award-info":[{"award-number":["19786"]}]},{"name":"AIRC","award":["813863"],"award-info":[{"award-number":["813863"]}]},{"DOI":"10.13039\/501100000780","name":"European Union\u2019s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie","doi-asserted-by":"publisher","award":["19786"],"award-info":[{"award-number":["19786"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union\u2019s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie","doi-asserted-by":"publisher","award":["813863"],"award-info":[{"award-number":["813863"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"name":"fellowship from the Istituto Nazionale per le Ricerche Cardiovascolari","award":["19786"],"award-info":[{"award-number":["19786"]}]},{"name":"fellowship from the Istituto Nazionale per le Ricerche Cardiovascolari","award":["813863"],"award-info":[{"award-number":["813863"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The mitochondrial protease Lonp1 is a multifunctional enzyme that regulates crucial mitochondrial functions, including the degradation of oxidized proteins, folding of imported proteins and maintenance the correct number of copies of mitochondrial DNA. A series of recent studies has put Lonp1 at the center of the stage in the homeostasis of cardiomyocytes and muscle skeletal cells. During heart development, Lonp1 allows the metabolic shift from anaerobic glycolysis to mitochondrial oxidative phosphorylation. Knock out of Lonp1 arrests heart development and determines cardiomyocyte apoptosis. In adults, Lonp1 acts as a cardioprotective protein, as its upregulation mitigates cardiac injury by preventing the oxidative damage of proteins and lipids, and by preserving mitochondrial redox balance. In skeletal muscle, Lonp1 is crucial for cell development, as it mediates the activation of PINK1\/Parkin pathway needed for proper myoblast differentiation. Skeletal muscle-specific ablation of Lonp1 in mice causes reduced muscle fiber size and strength due to the accumulation of mitochondrial-retained protein in muscle. Lonp1 expression and activity decline with age in different tissues, including skeletal muscle, and are associated with a functional decline and structural impairment of muscle fibers. Aerobic exercise increases unfolded protein response markers including Lonp1 in the skeletal muscle of aged animals and is associated with muscle functional recovery. Finally, mutations of Lonp1 cause a syndrome named CODAS (Cerebral, Ocular, Dental, Auricular, and Skeletal anomalies) characterized by the impaired development of multiple organs and tissues, including myocytes. CODAS patients show hypotonia and ptosis, indicative of skeletal muscle reduced performance. Overall, this body of observations points Lonp1 as a crucial regulator of mitochondrial functions in the heart and in skeletal muscle.<\/jats:p>","DOI":"10.3390\/antiox12030598","type":"journal-article","created":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T03:00:38Z","timestamp":1677553238000},"page":"598","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["The Role of Lonp1 on Mitochondrial Functions during Cardiovascular and Muscular Diseases"],"prefix":"10.3390","volume":"12","author":[{"given":"Giada","family":"Zanini","sequence":"first","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Selleri","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"},{"name":"Istituto Nazionale per le Ricerche Cardiovascolari, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Malerba","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kateryna","family":"Solodka","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"},{"name":"Istituto Nazionale per le Ricerche Cardiovascolari, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Sinigaglia","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3079-8001","authenticated-orcid":false,"given":"Milena","family":"Nasi","sequence":"additional","affiliation":[{"name":"Surgical, Medical and Dental Department of Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1487-9530","authenticated-orcid":false,"given":"Anna Vittoria","family":"Mattioli","sequence":"additional","affiliation":[{"name":"Istituto Nazionale per le Ricerche Cardiovascolari, 40126 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9118-1262","authenticated-orcid":false,"given":"Marcello","family":"Pinti","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1161\/CIRCRESAHA.112.268946","article-title":"Mitochondrial control of cellular life, stress, and death","volume":"111","author":"Galluzzi","year":"2012","journal-title":"Circ. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/nrcardio.2017.35","article-title":"Myocardial stress and autophagy: Mechanisms and potential therapies","volume":"14","author":"Delbridge","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/s41580-018-0052-8","article-title":"The machineries, regulation and cellular functions of mitochondrial calcium","volume":"19","author":"Giorgi","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41569-018-0074-0","article-title":"Targeting mitochondria for cardiovascular disorders: Therapeutic potential and obstacles","volume":"16","author":"Bonora","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1161\/RES.0000000000000104","article-title":"Mitochondrial Function, Biology, and Role in Disease: A Scientific Statement From the American Heart Association","volume":"118","author":"Murphy","year":"2016","journal-title":"Circ. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/nrcardio.2017.23","article-title":"Sarcoplasmic reticulum-mitochondria communication in cardiovascular pathophysiology","volume":"14","author":"Pennanen","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1161\/CIRCRESAHA.117.311082","article-title":"Autophagy and Mitophagy in Cardiovascular Disease","volume":"120","author":"Kroemer","year":"2017","journal-title":"Circ. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.exger.2004.01.005","article-title":"Myocyte aging and mitochondrial turnover","volume":"39","author":"Terman","year":"2004","journal-title":"Exp. Gerontol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1016\/j.bbabio.2016.03.025","article-title":"Emerging role of Lon protease as a master regulator of mitochondrial functions","volume":"1857","author":"Pinti","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"11247","DOI":"10.1073\/pnas.90.23.11247","article-title":"A human mitochondrial ATP-dependent protease that is highly homologous to bacterial Lon protease","volume":"90","author":"Wang","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/S0968-0004(97)01020-7","article-title":"ATP-dependent proteases that also chaperone protein biogenesis","volume":"22","author":"Suzuki","year":"1997","journal-title":"Trends Biochem. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.1128\/JB.184.13.3689-3698.2002","article-title":"A membrane-bound archaeal Lon protease displays ATP-independent proteolytic activity towards unfolded proteins and ATP-dependent activity for folded proteins","volume":"184","author":"Fukui","year":"2002","journal-title":"J. Bacteriol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4409","DOI":"10.1111\/bph.14045","article-title":"Lon protease: A novel mitochondrial matrix protein in the interconnection between drug-induced mitochondrial dysfunction and endoplasmic reticulum stress","volume":"174","author":"Polo","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"10877","DOI":"10.1038\/s41598-022-14860-0","article-title":"Evidence for mitochondrial Lonp1 expression in the nucleus","volume":"12","author":"Gibellini","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.bbamcr.2011.11.003","article-title":"Multitasking in the mitochondrion by the ATP-dependent Lon protease","volume":"1823","author":"Venkatesh","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.ircmb.2020.02.005","article-title":"The biology of Lonp1: More than a mitochondrial protease","volume":"354","author":"Gibellini","year":"2020","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e968505","DOI":"10.4161\/23723548.2014.968505","article-title":"Lon protease: A key enzyme controlling mitochondrial bioenergetics in cancer","volume":"1","author":"Quiros","year":"2014","journal-title":"Mol. Cell. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.molcel.2012.10.023","article-title":"Phosphorylation of human TFAM in mitochondria impairs DNA binding and promotes degradation by the AAA+ Lon protease","volume":"49","author":"Lu","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1074\/jbc.M116.754127","article-title":"Regulation of Pyruvate Dehydrogenase Kinase 4 in the Heart through Degradation by the Lon Protease in Response to Mitochondrial Substrate Availability","volume":"292","author":"Crewe","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41389-021-00306-1","article-title":"LONP1 and ClpP cooperatively regulate mitochondrial proteostasis for cancer cell survival","volume":"10","author":"Lee","year":"2021","journal-title":"Oncogenesis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4807","DOI":"10.1007\/s00018-015-2039-3","article-title":"Mitochondrial Lon protease at the crossroads of oxidative stress, ageing and cancer","volume":"72","author":"Pinti","year":"2015","journal-title":"Cell. Mol. Life. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"12679","DOI":"10.1073\/pnas.1308487110","article-title":"Oxygen-sensitive mitochondrial accumulation of cystathionine beta-synthase mediated by Lon protease","volume":"110","author":"Teng","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/ncb836","article-title":"Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATP-stimulated mechanism","volume":"4","author":"Bota","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.cell.2007.01.047","article-title":"HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells","volume":"129","author":"Fukuda","year":"2007","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.celrep.2014.06.018","article-title":"ATP-dependent Lon protease controls tumor bioenergetics by reprogramming mitochondrial activity","volume":"8","author":"Quiros","year":"2014","journal-title":"Cell Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.mito.2015.04.004","article-title":"Mitochondrial Lon protease controls ROS-dependent apoptosis in cardiomyocyte under hypoxia","volume":"23","author":"Kuo","year":"2015","journal-title":"Mitochondrion"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41467-020-20597-z","article-title":"LONP1 and mtHSP70 cooperate to promote mitochondrial protein folding","volume":"12","author":"Shin","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/s42003-021-02498-z","article-title":"Mitochondrial Lon protease is a gatekeeper for proteins newly imported into the matrix","volume":"4","author":"Matsushima","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e681","DOI":"10.1038\/cddis.2013.204","article-title":"Overexpression of Lon contributes to survival and aggressive phenotype of cancer cells through mitochondrial complex I-mediated generation of reactive oxygen species","volume":"4","author":"Cheng","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Zanini, G., Selleri, V., De Gaetano, A., Gibellini, L., Malerba, M., Mattioli, A.V., Nasi, M., Apostolova, N., and Pinti, M. (2022). Differential Expression of Lonp1 Isoforms in Cancer Cells. Cells, 11.","DOI":"10.3390\/cells11233940"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1038\/nrm3479","article-title":"Mitochondria: Master regulators of danger signalling","volume":"13","author":"Galluzzi","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/nature13392","article-title":"Ubiquitin is phosphorylated by PINK1 to activate parkin","volume":"510","author":"Koyano","year":"2014","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Thomas, R.E., Andrews, L.A., Burman, J.L., Lin, W.Y., and Pallanck, L.J. (2014). PINK1-Parkin pathway activity is regulated by degradation of PINK1 in the mitochondrial matrix. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004279"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/embor.2012.14","article-title":"Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment","volume":"13","author":"Greene","year":"2012","journal-title":"EMBO Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"151986","DOI":"10.1016\/j.acthis.2022.151986","article-title":"Inhibition of Lonp1 induces mitochondrial remodeling and autophagy suppression in cervical cancer cells","volume":"125","author":"Wang","year":"2023","journal-title":"Acta Histochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1093\/gerona\/glu004","article-title":"Downregulation of E3 ubiquitin ligases and mitophagy-related genes in skeletal muscle of physically inactive, frail older women: A cross-sectional comparison","volume":"69","author":"Drummond","year":"2014","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Leduc-Gaudet, J.P., Hussain, S.N.A., Barreiro, E., and Gouspillou, G. (2021). Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158179"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e1642","DOI":"10.1038\/cddis.2015.9","article-title":"Mitochondrial Lon regulates apoptosis through the association with Hsp60-mtHsp70 complex","volume":"6","author":"Kao","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1128\/IAI.00076-16","article-title":"The Protease Locus of Francisella tularensis LVS Is Required for Stress Tolerance and Infection in the Mammalian Host","volume":"84","author":"He","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1093\/nar\/gkm1140","article-title":"Thermodynamic characterization of specific interactions between the human Lon protease and G-quartet DNA","volume":"36","author":"Chen","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"17363","DOI":"10.1074\/jbc.M611540200","article-title":"Roles for the human ATP-dependent Lon protease in mitochondrial DNA maintenance","volume":"282","author":"Lu","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1038\/emboj.2009.412","article-title":"Quantitative and spatio-temporal features of protein aggregation in Escherichia coli and consequences on protein quality control and cellular ageing","volume":"29","author":"Winkler","year":"2010","journal-title":"EMBO J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"13902","DOI":"10.1074\/jbc.M309642200","article-title":"DNA and RNA binding by the mitochondrial lon protease is regulated by nucleotide and protein substrate","volume":"279","author":"Liu","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1002\/ajmg.a.37029","article-title":"Mutations in LONP1, a mitochondrial matrix protease, cause CODAS syndrome","volume":"167","author":"Dikoglu","year":"2015","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ajhg.2014.12.003","article-title":"CODAS syndrome is associated with mutations of LONP1, encoding mitochondrial AAA+ Lon protease","volume":"96","author":"Strauss","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1031856","DOI":"10.3389\/fgene.2022.1031856","article-title":"The first case report of CODAS syndrome in Chinese population caused by two LONP1 pathogenic mutations","volume":"13","author":"Tang","year":"2022","journal-title":"Front. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1002\/ajmg.a.33242","article-title":"Fourth case of cerebral, ocular, dental, auricular, skeletal syndrome (CODAS), description of new features and molecular analysis","volume":"152A","author":"Marlin","year":"2010","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1093\/hmg\/ddy351","article-title":"Bi-allelic mutations of LONP1 encoding the mitochondrial LonP1 protease cause pyruvate dehydrogenase deficiency and profound neurodegeneration with progressive cerebellar atrophy","volume":"28","author":"Nimmo","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1016\/j.ajhg.2021.08.011","article-title":"Rare and de novo variants in 827 congenital diaphragmatic hernia probands implicate LONP1 as candidate risk gene","volume":"108","author":"Qiao","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1152\/physiolgenomics.00177.2002","article-title":"In for the long run: Focus on \u201cLifelong voluntary exercise in the mouse prevents age-related alterations in gene expression in the heart\u201d","volume":"12","author":"Welle","year":"2003","journal-title":"Physiol. Genomics"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Chandel, N.S. (2014). Mitochondria as signaling organelles. BMC Biol., 12.","DOI":"10.1186\/1741-7007-12-34"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"491","DOI":"10.2217\/fca-2018-0045","article-title":"Type-2 diabetes mellitus and cardiovascular disease","volume":"14","author":"Henning","year":"2018","journal-title":"Future. Cardiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.3389\/fphys.2018.01514","article-title":"Diabetic Cardiomyopathy: Current and Future Therapies. Beyond Glycemic Control","volume":"9","author":"Borghetti","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"21630","DOI":"10.1002\/jcp.28821","article-title":"Impact of different ectopic fat depots on cardiovascular and metabolic diseases","volume":"234","author":"Ferrara","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.3389\/fphar.2019.01606","article-title":"Secondary Prevention Medical Therapy and Outcomes in Patients With Myocardial Infarction With Non-Obstructive Coronary Artery Disease","volume":"10","author":"Paolisso","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"729","DOI":"10.2147\/VHRM.S242636","article-title":"Subclinical Vascular Damage: Current Insights and Future Potential","volume":"17","author":"Mattioli","year":"2021","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4806","DOI":"10.2174\/1381612811319270003","article-title":"Cardiac dysfunction and oxidative stress in the metabolic syndrome: An update on antioxidant therapies","volume":"19","author":"Ilkun","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1089\/ars.2015.6294","article-title":"The mitochondria in diabetic heart failure: From pathogenesis to therapeutic promise","volume":"22","author":"Schilling","year":"2015","journal-title":"Antioxid. Redox. Signal."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/cdd.2008.13","article-title":"Role of hypoxia-inducible factor in cell survival during myocardial ischemia-reperfusion","volume":"15","author":"Loor","year":"2008","journal-title":"Cell Death Differ."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.freeradbiomed.2009.12.022","article-title":"Reactive oxygen species, cellular redox systems, and apoptosis","volume":"48","author":"Circu","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.yjmcc.2018.12.017","article-title":"Mitochondrial LonP1 protects cardiomyocytes from ischemia\/reperfusion injury in vivo","volume":"128","author":"Venkatesh","year":"2019","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"194233","DOI":"10.1242\/dev.194233","article-title":"The developing heart: From The Wizard of Oz to congenital heart disease","volume":"147","author":"Bruneau","year":"2020","journal-title":"Development"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.devcel.2016.11.012","article-title":"Myocardial VHL-HIF Signaling Controls an Embryonic Metabolic Switch Essential for Cardiac Maturation","volume":"39","author":"Escobar","year":"2016","journal-title":"Dev. Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1093\/cvr\/cvaa159","article-title":"The long and winding road of cardiomyocyte maturation","volume":"117","author":"Maroli","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e012731","DOI":"10.1161\/JAHA.119.012731","article-title":"Complex Regulation of Mitochondrial Function During Cardiac Development","volume":"8","author":"Zhao","year":"2019","journal-title":"J. Am. Heart. Assoc."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"De Gaetano, A., Gibellini, L., Bianchini, E., Borella, R., De Biasi, S., Nasi, M., Boraldi, F., Cossarizza, A., and Pinti, M. (2020). Impaired Mitochondrial Morphology and Functionality in Lonp1(wt\/-) Mice. J. Clin. Med., 9.","DOI":"10.3390\/jcm9061783"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"200458","DOI":"10.1242\/dev.200458","article-title":"LONP1-mediated mitochondrial quality control safeguards metabolic shifts in heart development","volume":"149","author":"Zhao","year":"2022","journal-title":"Development"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Crewe, C., Kinter, M., and Szweda, L.I. (2013). Rapid inhibition of pyruvate dehydrogenase: An initiating event in high dietary fat-induced loss of metabolic flexibility in the heart. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077280"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.jacc.2018.12.055","article-title":"Intercepting the Lipid-Induced Integrated Stress Response Reduces Atherosclerosis","volume":"73","author":"Onat","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1161\/CIRCHEARTFAILURE.113.001062","article-title":"Oxidative post-translational modifications develop LONP1 dysfunction in pressure overload heart failure","volume":"7","author":"Hoshino","year":"2014","journal-title":"Circ. Heart Fail."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"487","DOI":"10.2217\/fca-2021-0011","article-title":"Cardiovascular disease prevention and therapy in women with Type 2 diabetes","volume":"17","author":"Cocchi","year":"2021","journal-title":"Future Cardiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","article-title":"Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease","volume":"377","author":"Ridker","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.neuint.2008.06.004","article-title":"Inactivation of brain mitochondrial Lon protease by peroxynitrite precedes electron transport chain dysfunction","volume":"53","author":"Stanyer","year":"2008","journal-title":"Neurochem. Int."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.freeradbiomed.2010.04.001","article-title":"Proteomics study of oxidative stress and Src kinase inhibition in H9C2 cardiomyocytes: A cell model of heart ischemia-reperfusion injury and treatment","volume":"49","author":"Chou","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/1423-0127-20-86","article-title":"Epigallocatechin-3-gallate-mediated cardioprotection by Akt\/GSK-3beta\/caveolin signalling in H9c2 rat cardiomyoblasts","volume":"20","author":"Hsieh","year":"2013","journal-title":"J. Biomed. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1146\/annurev-physiol-021909-135929","article-title":"The cardiac mitochondrion: Nexus of stress","volume":"72","author":"Baines","year":"2010","journal-title":"Annu. Rev. Physiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1146\/annurev.physiol.010908.163111","article-title":"Cell death in the pathogenesis of heart disease: Mechanisms and significance","volume":"72","author":"Whelan","year":"2010","journal-title":"Annu. Rev. Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.bbagen.2006.06.006","article-title":"Short time exposure to hypoxia promotes H9c2 cell growth","volume":"1760","author":"Takahashi","year":"2006","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/j.1582-4934.2008.00495.x","article-title":"Cardioprotection by adaptation to ischaemia augments autophagy in association with BAG-1 protein","volume":"13","author":"Gurusamy","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1093\/cvr\/cvp384","article-title":"Cardioprotection by resveratrol: A novel mechanism via autophagy involving the mTORC2 pathway","volume":"86","author":"Gurusamy","year":"2010","journal-title":"Cardiovasc. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.freeradbiomed.2011.05.010","article-title":"Extending life span by increasing oxidative stress","volume":"51","author":"Ristow","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.exger.2010.03.014","article-title":"How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis)","volume":"45","author":"Ristow","year":"2010","journal-title":"Exp. Gerontol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ejvs.2004.11.005","article-title":"Ischaemic preconditioning protects against ischaemia\/reperfusion injury: Emerging concepts","volume":"29","author":"Pasupathy","year":"2005","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.mito.2019.10.004","article-title":"Cell stress management by the mitochondrial LonP1 protease\u2014Insights into mitigating developmental, oncogenic and cardiac stress","volume":"51","author":"Venkatesh","year":"2020","journal-title":"Mitochondrion"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1093\/cvr\/cvm035","article-title":"Complete loss of ischaemic preconditioning-induced cardioprotection in mice with partial deficiency of HIF-1 alpha","volume":"77","author":"Cai","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1161\/CIRCULATIONAHA.107.758516","article-title":"Hypoxia-inducible factor-1 is central to cardioprotection: A new paradigm for ischemic preconditioning","volume":"118","author":"Eckle","year":"2008","journal-title":"Circulation"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.mito.2010.09.010","article-title":"Functional characterization of the promoter of the human Lon protease gene","volume":"11","author":"Pinti","year":"2011","journal-title":"Mitochondrion"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.bbabio.2017.04.003","article-title":"Mitochondrial LON protease-dependent degradation of cytochrome c oxidase subunits under hypoxia and myocardial ischemia","volume":"1858","author":"Sepuri","year":"2017","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1111\/j.1742-4658.2008.06847.x","article-title":"Frataxin deficiency causes upregulation of mitochondrial Lon and ClpP proteases and severe loss of mitochondrial Fe-S proteins","volume":"276","author":"Guillon","year":"2009","journal-title":"FEBS J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1074\/jbc.M507741200","article-title":"Protein kinase A-mediated phosphorylation modulates cytochrome c oxidase function and augments hypoxia and myocardial ischemia-related injury","volume":"281","author":"Prabu","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1046\/j.1432-1033.2003.03447.x","article-title":"Adaptive changes in the expression of nuclear and mitochondrial encoded subunits of cytochrome c oxidase and the catalytic activity during hypoxia","volume":"270","author":"Vijayasarathy","year":"2003","journal-title":"Eur. J. Biochem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.mito.2011.06.001","article-title":"The role of mitochondrial membrane potential in ischemic heart failure","volume":"11","author":"Kadenbach","year":"2011","journal-title":"Mitochondrion"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/jcp.25413","article-title":"Targeted Modification of Mitochondrial ROS Production Converts High Glucose-Induced Cytotoxicity to Cytoprotection: Effects on Anesthetic Preconditioning","volume":"232","author":"Sedlic","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"5987","DOI":"10.1073\/pnas.0501519102","article-title":"Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia\/reperfusion","volume":"102","author":"Bulteau","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Cantu, D., Schaack, J., and Patel, M. (2009). Oxidative inactivation of mitochondrial aconitase results in iron and H2O2-mediated neurotoxicity in rat primary mesencephalic cultures. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007095"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1097\/FJC.0b013e3181e74a14","article-title":"Energy metabolic phenotype of the cardiomyocyte during development, differentiation, and postnatal maturation","volume":"56","author":"Lopaschuk","year":"2010","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1152\/physrev.00015.2009","article-title":"Myocardial fatty acid metabolism in health and disease","volume":"90","author":"Lopaschuk","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1152\/physrev.00006.2004","article-title":"Myocardial substrate metabolism in the normal and failing heart","volume":"85","author":"Stanley","year":"2005","journal-title":"Physiol. Rev."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1136\/hrt.2011.226332","article-title":"Effect of partial inhibition of fatty acid oxidation by trimetazidine on whole body energy metabolism in patients with chronic heart failure","volume":"97","author":"Fragasso","year":"2011","journal-title":"Heart"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1093\/cvr\/cvt216","article-title":"Failing mouse hearts utilize energy inefficiently and benefit from improved coupling of glycolysis and glucose oxidation","volume":"101","author":"Masoud","year":"2014","journal-title":"Cardiovasc. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1038\/s41467-022-28557-5","article-title":"Disuse-associated loss of the protease LONP1 in muscle impairs mitochondrial function and causes reduced skeletal muscle mass and strength","volume":"13","author":"Xu","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2258","DOI":"10.1093\/gerona\/glaa059","article-title":"Aerobic Exercise Training Induces the Mitonuclear Imbalance and UPRmt in the Skeletal Muscle of Aged Mice","volume":"75","author":"Cordeiro","year":"2020","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.arr.2005.04.001","article-title":"Functional senescence in Drosophila melanogaster","volume":"4","author":"Grotewiel","year":"2005","journal-title":"Ageing Res. Rev."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/dneu.20388","article-title":"Age-related changes in climbing behavior and neural circuit physiology in Drosophila","volume":"67","author":"Martinez","year":"2007","journal-title":"Dev. Neurobiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1529\/biophysj.108.130005","article-title":"Aging enhances indirect flight muscle fiber performance yet decreases flight ability in Drosophila","volume":"95","author":"Miller","year":"2008","journal-title":"Biophys. J."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"13920","DOI":"10.1093\/nar\/gku1132","article-title":"Drosophila melanogaster LRPPRC2 is involved in coordination of mitochondrial translation","volume":"42","author":"Baggio","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Bratic, A., Wredenberg, A., Gronke, S., Stewart, J.B., Mourier, A., Ruzzenente, B., Kukat, C., Wibom, R., Habermann, B., and Partridge, L. (2011). The bicoid stability factor controls polyadenylation and expression of specific mitochondrial mRNAs in Drosophila melanogaster. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002324"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1016\/j.celrep.2016.07.031","article-title":"Hierarchical RNA Processing Is Required for Mitochondrial Ribosome Assembly","volume":"16","author":"Rackham","year":"2016","journal-title":"Cell Rep."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41420-018-0110-1","article-title":"Lon protease inactivation in Drosophila causes unfolded protein stress and inhibition of mitochondrial translation","volume":"4","author":"Pareek","year":"2018","journal-title":"Cell Death. Discov."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1038\/s41419-020-03062-z","article-title":"Mitochondrial ClpP serine protease-biological function and emerging target for cancer therapy","volume":"11","author":"Nouri","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/jhg.2017.11","article-title":"A novel mutation in the proteolytic domain of LONP1 causes atypical CODAS syndrome","volume":"62","author":"Inui","year":"2017","journal-title":"J. Hum. Genet."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"981","DOI":"10.3389\/fneur.2019.00981","article-title":"Expanding the Clinical Spectrum of LONP1-Related Mitochondrial Cytopathy","volume":"10","author":"MacNeil","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.cmet.2009.10.008","article-title":"Autophagy is required to maintain muscle mass","volume":"10","author":"Masiero","year":"2009","journal-title":"Cell. Metab."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.tem.2013.09.004","article-title":"Skeletal muscle autophagy: A new metabolic regulator","volume":"24","author":"Neel","year":"2013","journal-title":"Trends. Endocrinol. Metab."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.cmet.2007.11.001","article-title":"FoxO3 controls autophagy in skeletal muscle in vivo","volume":"6","author":"Mammucari","year":"2007","journal-title":"Cell. Metab."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"C422","DOI":"10.1152\/ajpcell.00240.2012","article-title":"Adaptive plasticity of autophagic proteins to denervation in aging skeletal muscle","volume":"304","author":"Vainshtein","year":"2013","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13395-015-0033-y","article-title":"PGC-1alpha modulates denervation-induced mitophagy in skeletal muscle","volume":"5","author":"Vainshtein","year":"2015","journal-title":"Skelet. Muscle"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"C1020","DOI":"10.1152\/ajpcell.00589.2019","article-title":"LonP1 regulates mitochondrial network remodeling through the PINK1\/Parkin pathway during myoblast differentiation","volume":"319","author":"Huang","year":"2020","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"845379","DOI":"10.4061\/2011\/845379","article-title":"Morphofunctional and Biochemical Approaches for Studying Mitochondrial Changes during Myoblasts Differentiation","volume":"2011","author":"Barbieri","year":"2011","journal-title":"J. Aging Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"C474","DOI":"10.1152\/ajpcell.00112.2018","article-title":"Yap regulates mitochondrial structural remodeling during myoblast differentiation","volume":"315","author":"Huang","year":"2018","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1146\/annurev.cellbio.18.012502.105758","article-title":"Myogenic regulatory factors and the specification of muscle progenitors in vertebrate embryos","volume":"18","author":"Pownall","year":"2002","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Narendra, D.P., Jin, S.M., Tanaka, A., Suen, D.F., Gautier, C.A., Shen, J., Cookson, M.R., and Youle, R.J. (2010). PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol., 8.","DOI":"10.1371\/journal.pbio.1000298"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1080\/15548627.2019.1591672","article-title":"Mitophagy regulates mitochondrial network signaling, oxidative stress, and apoptosis during myoblast differentiation","volume":"15","author":"Baechler","year":"2019","journal-title":"Autophagy"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1080\/15548627.2015.1115172","article-title":"Mitophagy is required for mitochondrial biogenesis and myogenic differentiation of C2C12 myoblasts","volume":"12","author":"Sin","year":"2016","journal-title":"Autophagy"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1126\/science.1231031","article-title":"PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria","volume":"340","author":"Chen","year":"2013","journal-title":"Science"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"4861","DOI":"10.1093\/hmg\/ddq419","article-title":"Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1\/parkin-dependent manner upon induction of mitophagy","volume":"19","author":"Gegg","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"22938","DOI":"10.1074\/jbc.M109.035774","article-title":"Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation","volume":"284","author":"Lutz","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.15252\/embj.201593084","article-title":"Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway","volume":"35","author":"Sebastian","year":"2016","journal-title":"EMBO J."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"De Gaetano, A., Gibellini, L., Zanini, G., Nasi, M., Cossarizza, A., and Pinti, M. (2021). Mitophagy and Oxidative Stress: The Role of Aging. Antioxidants, 10.","DOI":"10.3390\/antiox10050794"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1126\/science.1065874","article-title":"Identification of ubiquitin ligases required for skeletal muscle atrophy","volume":"294","author":"Bodine","year":"2001","journal-title":"Science"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"14440","DOI":"10.1073\/pnas.251541198","article-title":"Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy","volume":"98","author":"Gomes","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1146\/annurev-pharmtox-010510-100537","article-title":"Molecular mechanisms and treatment options for muscle wasting diseases","volume":"51","author":"Ruegg","year":"2011","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/nrd4467","article-title":"Muscle wasting in disease: Molecular mechanisms and promising therapies","volume":"14","author":"Cohen","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"59","DOI":"10.3109\/10409238.2013.857291","article-title":"Signaling pathways controlling skeletal muscle mass","volume":"49","author":"Egerman","year":"2014","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"eabo0340","DOI":"10.1126\/sciadv.abo0340","article-title":"Mitochondrial proteostasis stress in muscle drives a long-range protective response to alleviate dietary obesity independently of ATF4","volume":"8","author":"Guo","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1038\/s41574-021-00529-7","article-title":"GDF15: Emerging biology and therapeutic applications for obesity and cardiometabolic disease","volume":"17","author":"Wang","year":"2021","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.tem.2021.08.008","article-title":"Stress-induced FGF21 and GDF15 in obesity and obesity resistance","volume":"32","author":"Keipert","year":"2021","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1172\/JCI23606","article-title":"FGF-21 as a novel metabolic regulator","volume":"115","author":"Kharitonenkov","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.cmet.2007.05.003","article-title":"Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21","volume":"5","author":"Inagaki","year":"2007","journal-title":"Cell Metab."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.cmet.2014.07.012","article-title":"FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss","volume":"20","author":"Owen","year":"2014","journal-title":"Cell Metab."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2016.23","article-title":"Mitonuclear communication in homeostasis and stress","volume":"17","author":"Quiros","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"e50094","DOI":"10.15252\/embr.202050094","article-title":"Systemic effects of mitochondrial stress","volume":"21","author":"Bolas","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nrm.2017.110","article-title":"The mitochondrial UPR: Mechanisms, physiological functions and implications in ageing","volume":"19","author":"Shpilka","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.tcb.2020.03.001","article-title":"Folding the Mitochondrial UPR into the Integrated Stress Response","volume":"30","author":"Anderson","year":"2020","journal-title":"Trends. Cell Biol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"eabf0971","DOI":"10.1126\/sciadv.abf0971","article-title":"Adaptation to mitochondrial stress requires CHOP-directed tuning of ISR","volume":"7","author":"Kaspar","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1083\/jcb.201702058","article-title":"Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals","volume":"216","author":"Quiros","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"4559","DOI":"10.1111\/j.1432-1033.2004.04422.x","article-title":"Age-related impairment of mitochondrial matrix aconitase and ATP-stimulated protease in rat liver and heart","volume":"271","author":"Delaval","year":"2004","journal-title":"Eur. J. Biochem."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1046\/j.1432-1033.2003.03598.x","article-title":"Changes in rat liver mitochondria with aging. Lon protease-like reactivity and N(epsilon)-carboxymethyllysine accumulation in the matrix","volume":"270","author":"Bakala","year":"2003","journal-title":"Eur. J. Biochem."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1196\/annals.1404.015","article-title":"Importance of the lon protease in mitochondrial maintenance and the significance of declining lon in aging","volume":"1119","author":"Ngo","year":"2007","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.freeradbiomed.2012.11.019","article-title":"Deletion of the mitochondrial Pim1\/Lon protease in yeast results in accelerated aging and impairment of the proteasome","volume":"56","author":"Erjavec","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Taouktsi, E., Kyriakou, E., Smyrniotis, S., Borbolis, F., Bondi, L., Avgeris, S., Trigazis, E., Rigas, S., Voutsinas, G.E., and Syntichaki, P. (2022). Organismal and Cellular Stress Responses upon Disruption of Mitochondrial Lonp1 Protease. Cells, 11.","DOI":"10.3390\/cells11081363"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/ncb1893","article-title":"Increasing organismal healthspan by enhancing mitochondrial protein quality control","volume":"11","author":"Luce","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1038\/s41419-018-1213-6","article-title":"Inactivation of Lon protease reveals a link between mitochondrial unfolded protein stress and mitochondrial translation inhibition","volume":"9","author":"Pareek","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cub.2016.10.044","article-title":"The Mitochondrial Lon Protease Is Required for Age-Specific and Sex-Specific Adaptation to Oxidative Stress","volume":"27","author":"Pomatto","year":"2017","journal-title":"Curr. Biol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"3265","DOI":"10.1074\/jbc.M111.280156","article-title":"Mitophagy plays an essential role in reducing mitochondrial production of reactive oxygen species and mutation of mitochondrial DNA by maintaining mitochondrial quantity and quality in yeast","volume":"287","author":"Kurihara","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1096\/fj.04-3535fje","article-title":"Long-term caloric restriction abrogates the age-related decline in skeletal muscle aerobic function","volume":"19","author":"Hepple","year":"2005","journal-title":"FASEB J."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2933","DOI":"10.2337\/db08-0349","article-title":"Endurance exercise as a countermeasure for aging","volume":"57","author":"Lanza","year":"2008","journal-title":"Diabetes"},{"key":"ref_158","first-page":"64","article-title":"Protein modification in aging","volume":"62","author":"Stadtman","year":"1992","journal-title":"EXS"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/j.1474-9726.2005.00156.x","article-title":"Age-related changes in regional brain mitochondria from Fischer 344 rats","volume":"4","author":"LaFrance","year":"2005","journal-title":"Aging. Cell."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/aja.1001500105","article-title":"Ultrastructure of the aging myocardium: A morphometric approach","volume":"150","author":"Sachs","year":"1977","journal-title":"Am. J. Anat."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/1357-2725(95)00025-K","article-title":"Oxidative damage to mitochondrial DNA and its relationship to ageing","volume":"27","author":"Richter","year":"1995","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/S0891-5849(00)00317-8","article-title":"Mitochondrial free radical generation, oxidative stress, and aging","volume":"29","author":"Cadenas","year":"2000","journal-title":"Free Radic. Biol. Med."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1093\/nar\/27.11.2434","article-title":"Cell-by-cell scanning of whole mitochondrial genomes in aged human heart reveals a significant fraction of myocytes with clonally expanded deletions","volume":"27","author":"Khrapko","year":"1999","journal-title":"Nucleic Acids Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1111\/j.1749-6632.2002.tb02111.x","article-title":"Mitochondrial DNA deletion mutations and sarcopenia","volume":"959","author":"Aiken","year":"2002","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1159\/000212145","article-title":"Ageing changes in mammalian skeletal muscle: Biochemical studies","volume":"22","author":"Ermini","year":"1976","journal-title":"Gerontology"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"R127","DOI":"10.1152\/ajpregu.00337.2011","article-title":"Age-associated declines in mitochondrial biogenesis and protein quality control factors are minimized by exercise training","volume":"303","author":"Koltai","year":"2012","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.freeradbiomed.2016.06.031","article-title":"Mitochondrial Lon protease in human disease and aging: Including an etiologic classification of Lon-related diseases and disorders","volume":"100","author":"Bota","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.mito.2014.08.001","article-title":"Sirtuin 3 interacts with Lon protease and regulates its acetylation status","volume":"18","author":"Gibellini","year":"2014","journal-title":"Mitochondrion"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1210\/me.2005-0458","article-title":"Turnover of mitochondrial steroidogenic acute regulatory (StAR) protein by Lon protease: The unexpected effect of proteasome inhibitors","volume":"21","author":"Granot","year":"2007","journal-title":"Mol. Endocrinol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/3\/598\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:43:40Z","timestamp":1760121820000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/3\/598"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,28]]},"references-count":169,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["antiox12030598"],"URL":"https:\/\/doi.org\/10.3390\/antiox12030598","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,28]]}}}