{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:34:18Z","timestamp":1790836458069,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T00:00:00Z","timestamp":1600819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["ME1922\/17-1"],"award-info":[{"award-number":["ME1922\/17-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G.0A34.16N"],"award-info":[{"award-number":["G.0A34.16N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G.0901.18"],"award-info":[{"award-number":["G.0901.18"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004497","name":"Onderzoeksraad, KU Leuven","doi-asserted-by":"publisher","award":["C14\/19\/099"],"award-info":[{"award-number":["C14\/19\/099"]}],"id":[{"id":"10.13039\/501100004497","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The Transmembrane Bax Inhibitor-1 motif (TMBIM)-containing protein family is evolutionarily conserved and has been implicated in cell death susceptibility. The only member with a mitochondrial localization is TMBIM5 (also known as GHITM or MICS1), which affects cristae organization and associates with the Parkinson\u2019s disease-associated protein CHCHD2 in the inner mitochondrial membrane. We here used CRISPR-Cas9-mediated knockout HAP1 cells to shed further light on the function of TMBIM5 in physiology and cell death susceptibility. We found that compared to wild type, TMBIM5-knockout cells were smaller and had a slower proliferation rate. In these cells, mitochondria were more fragmented with a vacuolar cristae structure. In addition, the mitochondrial membrane potential was reduced and respiration was attenuated, leading to a reduced mitochondrial ATP generation. TMBIM5 did not associate with Mic10 and Mic60, which are proteins of the mitochondrial contact site and cristae organizing system (MICOS), nor did TMBIM5 knockout affect their expression levels. TMBIM5-knockout cells were more sensitive to apoptosis elicited by staurosporine and BH3 mimetic inhibitors of Bcl-2 and Bcl-XL. An unbiased proteomic comparison identified a dramatic downregulation of proteins involved in the mitochondrial protein synthesis machinery in TMBIM5-knockout cells. We conclude that TMBIM5 is important to maintain the mitochondrial structure and function possibly through the control of mitochondrial biogenesis.<\/jats:p>","DOI":"10.3390\/cells9102147","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T02:56:43Z","timestamp":1600916203000},"page":"2147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Transmembrane BAX Inhibitor-1 Motif Containing Protein 5 (TMBIM5) Sustains Mitochondrial Structure, Shape, and Function by Impacting the Mitochondrial Protein Synthesis Machinery"],"prefix":"10.3390","volume":"9","author":[{"given":"Bruno","family":"Seitaj","sequence":"first","affiliation":[{"name":"KU Leuven, Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine and Leuven Kanker Instituut (LKI), Campus Gasthuisberg ON-I Bus 802, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicia","family":"Maull","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine, Johannes Gutenberg University Medical Center Mainz, D-55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine, Johannes Gutenberg University Medical Center Mainz, D-55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"W\u00fcllner","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine, Johannes Gutenberg University Medical Center Mainz, D-55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6163-1995","authenticated-orcid":false,"given":"Christina","family":"Wolf","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine, Johannes Gutenberg University Medical Center Mainz, D-55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Schippers","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine, Johannes Gutenberg University Medical Center Mainz, D-55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"La Rovere","sequence":"additional","affiliation":[{"name":"KU Leuven, Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine and Leuven Kanker Instituut (LKI), Campus Gasthuisberg ON-I Bus 802, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8031-6384","authenticated-orcid":false,"given":"Ute","family":"Distler","sequence":"additional","affiliation":[{"name":"Institute for Immunology, Langenbeckstr. 1, D-55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3034-0017","authenticated-orcid":false,"given":"Stefan","family":"Tenzer","sequence":"additional","affiliation":[{"name":"Institute for Immunology, Langenbeckstr. 1, D-55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3591-4967","authenticated-orcid":false,"given":"Jan B.","family":"Parys","sequence":"additional","affiliation":[{"name":"KU Leuven, Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine and Leuven Kanker Instituut (LKI), Campus Gasthuisberg ON-I Bus 802, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5968-4828","authenticated-orcid":false,"given":"Geert","family":"Bultynck","sequence":"additional","affiliation":[{"name":"KU Leuven, Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine and Leuven Kanker Instituut (LKI), Campus Gasthuisberg ON-I Bus 802, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8774-0057","authenticated-orcid":false,"given":"Axel","family":"Methner","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine, Johannes Gutenberg University Medical Center Mainz, D-55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1016\/j.bbamcr.2015.03.002","article-title":"The transmembrane Bax inhibitor motif (TMBIM) containing protein family: Tissue expression, intracellular localization and effects on the ER Ca2+-filling state","volume":"1853","author":"Lisak","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1266\/ggs.81.41","article-title":"RECS1 deficiency in mice induces susceptibility to cystic medial degeneration","volume":"81","author":"Zhao","year":"2006","journal-title":"Genes Genet. Syst."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1007\/s10495-010-0556-y","article-title":"A shear stress responsive gene product PP1201 protects against Fas-mediated apoptosis by reducing Fas expression on the cell surface","volume":"16","author":"Shukla","year":"2011","journal-title":"Apoptosis"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12667","DOI":"10.1073\/pnas.96.22.12667","article-title":"LFG: An anti-apoptotic gene that provides protection from Fas-mediated cell death","volume":"96","author":"Somia","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/j.1471-4159.2007.04767.x","article-title":"Lifeguard\/neuronal membrane protein 35 regulates Fas ligand-mediated apoptosis in neurons via microdomain recruitment","volume":"103","author":"Fernandez","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0169-328X(02)00445-X","article-title":"Neural membrane protein 35\/Lifeguard is localized at postsynaptic sites and in dendrites","volume":"107","author":"Schweitzer","year":"2002","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1006\/mcne.1998.0697","article-title":"Neural membrane protein 35 (NMP35): A novel member of a gene family which is highly expressed in the adult nervous system","volume":"11","author":"Schweitzer","year":"1998","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/354070a0","article-title":"Cloning of cDNA for the glutamate-binding subunit of an NMDA receptor complex","volume":"354","author":"Kumar","year":"1991","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1038\/cdd.2011.189","article-title":"TMBIM3\/GRINA is a novel unfolded protein response (UPR) target gene that controls apoptosis through the modulation of ER calcium homeostasis","volume":"19","author":"Armisen","year":"2012","journal-title":"Cell Death Differ."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s11010-011-0877-3","article-title":"Mouse transmembrane BAX inhibitor motif 3 (Tmbim3) encodes a 38 kDa transmembrane protein expressed in the central nervous system","volume":"357","author":"Nielsen","year":"2011","journal-title":"Mol. Cell. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"D746","DOI":"10.1093\/nar\/gkv1045","article-title":"Expression Atlas update--an integrated database of gene and protein expression in humans, animals and plants","volume":"44","author":"Petryszak","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101361","DOI":"10.1016\/j.redox.2019.101361","article-title":"Stimulation of cell invasion by the Golgi Ion Channel GAAP\/TMBIM4 via an H2O2-Dependent Mechanism","volume":"28","author":"Almeida","year":"2020","journal-title":"Redox. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1083\/jcb.201301016","article-title":"hGAAP promotes cell adhesion and migration via the stimulation of store-operated Ca2+ entry and calpain 2","volume":"202","author":"Saraiva","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.bbrc.2005.12.141","article-title":"Ghitm is an ortholog of the Bombyx mori prothoracic gland-derived receptor (Pgdr) that is ubiquitously expressed in mammalian cells and requires an N-terminal signal sequence for expression","volume":"341","author":"Yoshida","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1091\/mbc.e07-12-1205","article-title":"Identification of a novel protein MICS1 that is involved in maintenance of mitochondrial morphology and apoptotic release of cytochrome c","volume":"19","author":"Oka","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S1097-2765(00)80034-9","article-title":"Bax inhibitor-1, a mammalian apoptosis suppressor identified by functional screening in yeast","volume":"1","author":"Xu","year":"1998","journal-title":"Mol. Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.molcel.2004.06.038","article-title":"BI-1 regulates an apoptosis pathway linked to endoplasmic reticulum stress","volume":"15","author":"Chae","year":"2004","journal-title":"Mol. Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.1073\/pnas.0506854103","article-title":"Cytoprotective gene bi-1 is required for intrinsic protection from endoplasmic reticulum stress and ischemia-reperfusion injury","volume":"103","author":"Fondevila","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/sj.cdd.4401547","article-title":"BI-1 protects cells from oxygen glucose deprivation by reducing the calcium content of the endoplasmic reticulum","volume":"12","author":"Westphalen","year":"2005","journal-title":"Cell Death Differ."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1074\/jbc.M111.275354","article-title":"The C terminus of Bax inhibitor-1 forms a Ca2+-permeable channel pore","volume":"287","author":"Bultynck","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"pe22","DOI":"10.1126\/scisignal.2005764","article-title":"Bax inhibitor-1 is likely a pH-sensitive calcium leak channel, not a H+\/Ca2+ exchanger","volume":"7","author":"Bultynck","year":"2014","journal-title":"Sci. Signal."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"15896","DOI":"10.1074\/jbc.M111.336149","article-title":"Six-transmembrane topology for Golgi anti-apoptotic protein (GAAP) and Bax inhibitor 1 (BI-1) provides model for the transmembrane Bax inhibitor-containing motif (TMBIM) family","volume":"287","author":"Carrara","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/onc.2014.6","article-title":"TMBIM protein family: Ancestral regulators of cell death","volume":"34","author":"Hetz","year":"2015","journal-title":"Oncogene"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.gene.2003.09.011","article-title":"Evolutionarily conserved cytoprotection provided by Bax Inhibitor-1 homologs from animals, plants, and yeast","volume":"323","author":"Chae","year":"2003","journal-title":"Gene"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1210\/endo.142.7.8233","article-title":"Identification, isolation, and cloning of growth hormone (GH)-inducible interscapular brown adipose complementary deoxyribonucleic acid from GH antagonist mice","volume":"142","author":"Li","year":"2001","journal-title":"Endocrinology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"471","DOI":"10.7150\/ijbs.3.471","article-title":"The growth-hormone inducible transmembrane protein (Ghitm) belongs to the Bax inhibitory protein-like family","volume":"3","author":"Reimers","year":"2007","journal-title":"Int. J. Biol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/0092-8674(95)90430-1","article-title":"Decoding of cytosolic calcium oscillations in the mitochondria","volume":"82","author":"Hajnoczky","year":"1995","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1146\/annurev-genom-082509-141720","article-title":"The mitochondrial proteome and human disease","volume":"11","author":"Calvo","year":"2010","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/nprot.2006.478","article-title":"Organelle isolation: Functional mitochondria from mouse liver, muscle and cultured fibroblasts","volume":"2","author":"Frezza","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1016\/j.celrep.2018.10.037","article-title":"MICU1 Confers Protection from MCU-Dependent Manganese Toxicity","volume":"25","author":"Wettmarshausen","year":"2018","journal-title":"Cell Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"39618","DOI":"10.1038\/srep39618","article-title":"BTeam, a Novel BRET-based Biosensor for the Accurate Quantification of ATP Concentration within Living Cells","volume":"6","author":"Yoshida","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4060","DOI":"10.1021\/acs.jproteome.7b00433","article-title":"Evaluation of FASP, SP3, and iST Protocols for Proteomic Sample Preparation in the Low Microgram Range","volume":"16","author":"Sielaff","year":"2017","journal-title":"J. Proteome Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/nmeth.2767","article-title":"Drift time-specific collision energies enable deep-coverage data-independent acquisition proteomics","volume":"11","author":"Distler","year":"2014","journal-title":"Nat. Methods"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1038\/nprot.2016.042","article-title":"Label-free quantification in ion mobility-enhanced data-independent acquisition proteomics","volume":"11","author":"Distler","year":"2016","journal-title":"Nat. Protoc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1101\/gr.177220.114","article-title":"Megabase-scale deletion using CRISPR\/Cas9 to generate a fully haploid human cell line","volume":"24","author":"Essletzbichler","year":"2014","journal-title":"Genome Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.cell.2013.08.032","article-title":"Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency","volume":"155","author":"Cogliati","year":"2013","journal-title":"Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.resp.2010.08.004","article-title":"Mitochondrial complex III: An essential component of universal oxygen sensing machinery?","volume":"174","author":"Chandel","year":"2010","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Porter, G.A., and Beutner, G. (2018). Cyclophilin D, Somehow a Master Regulator of Mitochondrial Function. Biomolecules, 8.","DOI":"10.3390\/biom8040176"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4356","DOI":"10.1038\/emboj.2011.379","article-title":"The mitochondrial contact site complex, a determinant of mitochondrial architecture","volume":"30","author":"Harner","year":"2011","journal-title":"EMBO J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.cmet.2015.04.007","article-title":"Central role of Mic10 in the mitochondrial contact site and cristae organizing system","volume":"21","author":"Bohnert","year":"2015","journal-title":"Cell Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1083\/jcb.201609046","article-title":"The MICOS component Mic60 displays a conserved membrane-bending activity that is necessary for normal cristae morphology","volume":"216","author":"Tarasenko","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"W160","DOI":"10.1093\/nar\/gkv455","article-title":"ProtPhylo: Identification of protein-phenotype and protein-protein functional associations via phylogenetic profiling","volume":"43","author":"Cheng","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Guarani, V., Jardel, C., Chretien, D., Lombes, A., Benit, P., Labasse, C., Lacene, E., Bourillon, A., Imbard, A., and Benoist, J.F. (2016). QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease. eLife, 5.","DOI":"10.7554\/eLife.17163"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/cdd.2017.183","article-title":"Why do BCL-2 inhibitors work and where should we use them in the clinic?","volume":"25","author":"Montero","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/cdd.2017.161","article-title":"The BCL-2 arbiters of apoptosis and their growing role as cancer targets","volume":"25","author":"Adams","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.trecan.2016.07.001","article-title":"Targeting BCL-2-like Proteins to Kill Cancer Cells","volume":"2","author":"Cory","year":"2016","journal-title":"Trends Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/nm.3048","article-title":"ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets","volume":"19","author":"Souers","year":"2013","journal-title":"Nat. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1021\/ml5001867","article-title":"Discovery of a Potent and Selective BCL-XL Inhibitor with in Vivo Activity","volume":"5","author":"Tao","year":"2014","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1038\/s41418-019-0391-9","article-title":"BH3 profiling discriminates on-target small molecule BH3 mimetics from putative mimetics","volume":"27","author":"Ryan","year":"2020","journal-title":"Cell Death Differ."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1080\/15384101.2015.1010973","article-title":"Inside the tumor: P53 modulates calcium homeostasis","volume":"14","author":"Giorgi","year":"2015","journal-title":"Cell Cycle"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nrm2147","article-title":"p53 in health and disease","volume":"8","author":"Vousden","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"148","DOI":"10.2174\/156652408783769562","article-title":"The Bax Inhibitor-1 (BI-1) family in apoptosis and tumorigenesis","volume":"8","author":"Reimers","year":"2008","journal-title":"Curr. Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"11785","DOI":"10.1074\/jbc.M115.637306","article-title":"Golgi anti-apoptotic proteins are highly conserved ion channels that affect apoptosis and cell migration","volume":"290","author":"Carrara","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.str.2019.03.003","article-title":"Ion and pH Sensitivity of a TMBIM Ca2+ Channel","volume":"27","author":"Guo","year":"2019","journal-title":"Structure"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1002\/embr.201338240","article-title":"Membrane depolarization activates the mitochondrial protease OMA1 by stimulating self-cleavage","volume":"15","author":"Zhang","year":"2014","journal-title":"EMBO Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.cell.2006.06.025","article-title":"OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion","volume":"126","author":"Frezza","year":"2006","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"14782","DOI":"10.1073\/pnas.1417253111","article-title":"Activation of mitochondrial protease OMA1 by Bax and Bak promotes cytochrome c release during apoptosis","volume":"111","author":"Jiang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"15500","DOI":"10.1038\/ncomms15500","article-title":"Loss of Parkinson\u2019s disease-associated protein CHCHD2 affects mitochondrial crista structure and destabilizes cytochrome c","volume":"8","author":"Meng","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.jmb.2009.08.041","article-title":"Systematic analysis of the twin cx(9)c protein family","volume":"393","author":"Longen","year":"2009","journal-title":"J. Mol. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1093\/hmg\/ddy413","article-title":"PD-linked CHCHD2 mutations impair CHCHD10 and a MICOS complex leading to mitochondria dysfunction","volume":"28","author":"Zhou","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Yu, W., Zhang, B., Song, H., Zhan, R., Li, L., He, C., Jiang, Q., Wang, X., Wei, L., and Zhao, N. (2020). Preliminary investigation demonstrating the GHITM gene probably involved in apoptosis and growth of the golden apple snail (Pomacea canaliculata). BMC Genom., 21.","DOI":"10.1186\/s12864-019-6434-2"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1126\/science.aan2507","article-title":"A pathology atlas of the human cancer transcriptome","volume":"357","author":"Uhlen","year":"2017","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1038\/cdd.2017.82","article-title":"BCL-2 family: Integrating stress responses at the ER to control cell demise","volume":"24","author":"Pihan","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_64","first-page":"521","article-title":"The inhibition of cg2076 the ghitm homologue inneurons of drosophila melanogaster can be rescued by buffy","volume":"12","author":"Staveley","year":"2016","journal-title":"J. RNA Genom."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1073\/pnas.1811938116","article-title":"PARL deficiency in mouse causes Complex III defects, coenzyme Q depletion, and Leigh-like syndrome","volume":"116","author":"Spinazzi","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"30307","DOI":"10.1074\/jbc.M403607200","article-title":"The LETM1\/YOL027 gene family encodes a factor of the mitochondrial K+ homeostasis with a potential role in the Wolf-Hirschhorn syndrome","volume":"279","author":"Nowikovsky","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1126\/science.1175145","article-title":"Genome-wide RNAi screen identifies Letm1 as a mitochondrial Ca2+\/H+ antiporter","volume":"326","author":"Jiang","year":"2009","journal-title":"Science"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1083\/jcb.200505060","article-title":"Mdm38 interacts with ribosomes and is a component of the mitochondrial protein export machinery","volume":"172","author":"Frazier","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1111\/j.1600-0854.2011.01239.x","article-title":"Mdm38 is a 14-3-3-like receptor and associates with the protein synthesis machinery at the inner mitochondrial membrane","volume":"12","author":"Lupo","year":"2011","journal-title":"Traffic"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Durigon, R., Mitchell, A.L., Jones, A.W., Manole, A., Mennuni, M., Hirst, E.M., Houlden, H., Maragni, G., Lattante, S., and Doronzio, P.N. (2018). LETM1 couples mitochondrial DNA metabolism and nutrient preference. EMBO Mol. Med., 10.","DOI":"10.15252\/emmm.201708550"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/10\/2147\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:12:44Z","timestamp":1760177564000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/10\/2147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,23]]},"references-count":70,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["cells9102147"],"URL":"https:\/\/doi.org\/10.3390\/cells9102147","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,23]]}}}