{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:19:21Z","timestamp":1771633161946,"version":"3.50.1"},"reference-count":104,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"National Funds through FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, I.P.","doi-asserted-by":"publisher","award":["UIDB\/04293\/2020"],"award-info":[{"award-number":["UIDB\/04293\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"National Funds through FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, I.P.","doi-asserted-by":"publisher","award":["ED481B-2023-005"],"award-info":[{"award-number":["ED481B-2023-005"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"National Funds through FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, I.P.","doi-asserted-by":"publisher","award":["ED431C 2022\/03-GRC Competitive Reference Group"],"award-info":[{"award-number":["ED431C 2022\/03-GRC Competitive Reference Group"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008425","name":"Conseller\u00eda de Cultura, educaci\u00f3n, Formaci\u00f3n Profesional e Universidades da Xunta de Galicia","doi-asserted-by":"publisher","award":["UIDB\/04293\/2020"],"award-info":[{"award-number":["UIDB\/04293\/2020"]}],"id":[{"id":"10.13039\/501100008425","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008425","name":"Conseller\u00eda de Cultura, educaci\u00f3n, Formaci\u00f3n Profesional e Universidades da Xunta de Galicia","doi-asserted-by":"publisher","award":["ED481B-2023-005"],"award-info":[{"award-number":["ED481B-2023-005"]}],"id":[{"id":"10.13039\/501100008425","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008425","name":"Conseller\u00eda de Cultura, educaci\u00f3n, Formaci\u00f3n Profesional e Universidades da Xunta de Galicia","doi-asserted-by":"publisher","award":["ED431C 2022\/03-GRC Competitive Reference Group"],"award-info":[{"award-number":["ED431C 2022\/03-GRC Competitive Reference Group"]}],"id":[{"id":"10.13039\/501100008425","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011596","name":"Conseller\u00eda de Educaci\u00f3n, Universidades e Formaci\u00f3n Profesional (Xunta de Galicia)","doi-asserted-by":"publisher","award":["UIDB\/04293\/2020"],"award-info":[{"award-number":["UIDB\/04293\/2020"]}],"id":[{"id":"10.13039\/501100011596","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011596","name":"Conseller\u00eda de Educaci\u00f3n, Universidades e Formaci\u00f3n Profesional (Xunta de Galicia)","doi-asserted-by":"publisher","award":["ED481B-2023-005"],"award-info":[{"award-number":["ED481B-2023-005"]}],"id":[{"id":"10.13039\/501100011596","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011596","name":"Conseller\u00eda de Educaci\u00f3n, Universidades e Formaci\u00f3n Profesional (Xunta de Galicia)","doi-asserted-by":"publisher","award":["ED431C 2022\/03-GRC Competitive Reference Group"],"award-info":[{"award-number":["ED431C 2022\/03-GRC Competitive Reference Group"]}],"id":[{"id":"10.13039\/501100011596","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dysfunctional mitochondria are present in many neurodegenerative diseases, such as spinocerebellar ataxia type 3 (SCA3), also known as Machado\u2013Joseph disease (MJD). SCA3\/MJD, the most frequent neurodegenerative ataxia worldwide, is caused by the abnormal expansion of the polyglutamine tract (polyQ) at ataxin-3. This protein is known to deubiquitinate key proteins such as Parkin, which is required for mitophagy. Ataxin-3 also interacts with Beclin1 (essential for initiating autophagosome formation adjacent to mitochondria), as well as with the mitochondrial cristae protein TBK1. To identify other proteins of the mitophagy pathway (according to the KEGG database) that can interact with ataxin-3, here we developed a pipeline for in silico analyses of protein\u2013protein interactions (PPIs), called auto-p2docking. Containerized in Docker, auto-p2docking ensures reproducibility and reduces the number of errors through its simplified configuration. Its architecture consists of 22 modules, here used to develop 12 protocols but that can be specified according to user needs. In this work, we identify 45 mitophagy proteins as putative ataxin-3 interactors (53% are novel), using ataxin-3 interacting regions for validation. Furthermore, we predict that ataxin-3 interactors from both Parkin-independent and -dependent mechanisms are affected by the polyQ expansion.<\/jats:p>","DOI":"10.3390\/ijms26031325","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T10:57:53Z","timestamp":1738666673000},"page":"1325","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Predicting Which Mitophagy Proteins Are Dysregulated in Spinocerebellar Ataxia Type 3 (SCA3) Using the Auto-p2docking Pipeline"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7032-5220","authenticated-orcid":false,"given":"Jorge","family":"Vieira","sequence":"first","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Instituto de Biologia Molecular e Celular (IBMC), Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"}]},{"given":"Mariana","family":"Barros","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Faculdade de Ci\u00eancias, Universidade do Porto, Rua do Campo Alegre s\/n, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6476-7206","authenticated-orcid":false,"given":"Hugo","family":"L\u00f3pez-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Computer Science, CINBIO, ESEI\u2014Escuela Superior de Ingenier\u00eda Inform\u00e1tica, Universidade de Vigo, 32004 Ourense, Spain"},{"name":"SING Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, 36213 Vigo, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6129-7245","authenticated-orcid":false,"given":"Daniel","family":"Glez-Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Department of Computer Science, CINBIO, ESEI\u2014Escuela Superior de Ingenier\u00eda Inform\u00e1tica, Universidade de Vigo, 32004 Ourense, Spain"},{"name":"SING Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, 36213 Vigo, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5991-7698","authenticated-orcid":false,"given":"Alba","family":"Nogueira-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Department of Computer Science, CINBIO, ESEI\u2014Escuela Superior de Ingenier\u00eda Inform\u00e1tica, Universidade de Vigo, 32004 Ourense, Spain"},{"name":"SING Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, 36213 Vigo, Spain"}]},{"given":"Cristina P.","family":"Vieira","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Instituto de Biologia Molecular e Celular (IBMC), Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1750-1172-6-35","article-title":"Machado-Joseph Disease: From first descriptions to new perspectives","volume":"6","author":"Bettencourt","year":"2011","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_2","first-page":"139","article-title":"Compromised mitochondrial complex II in models of Machado\u2013Joseph disease","volume":"1822","author":"Oliveira","year":"2011","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Basis Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1159\/000358801","article-title":"The Global Epidemiology of Hereditary Ataxia and Spastic Paraplegia: A Systematic Review of Prevalence Studies","volume":"42","author":"Ruano","year":"2014","journal-title":"Neuroepidemiology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/ng1194-221","article-title":"CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1","volume":"8","author":"Kawaguchi","year":"1994","journal-title":"Nat. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/jnc.14541","article-title":"Machado\u2013Joseph disease\/spinocerebellar ataxia type 3: Lessons from disease pathogenesis and clues into therapy","volume":"148","author":"Matos","year":"2018","journal-title":"J. Neurochem."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Totzeck, F., Andrade-Navarro, M.A., and Mier, P. (2017). The Protein Structure Context of PolyQ Regions. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0170801"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Sousa e Silva, R., Sousa, A.D., Vieira, J., and Vieira, C.P. (2023). The Josephin domain (JD) containing proteins are predicted to bind to the same interactors: Implications for spinocerebellar ataxia type 3 (SCA3) studies using Drosophila melanogaster mutants. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1140719"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Rocha, S., Vieira, J., V\u00e1zquez, N., L\u00f3pez-Fern\u00e1ndez, H., Fdez-Riverola, F., Reboiro-Jato, M., Sousa, A.D., and Vieira, C.P. (2019). ATXN1 N-terminal region explains the binding differences of wild-type and expanded forms. BMC Med Genom., 12.","DOI":"10.1186\/s12920-019-0594-4"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0896-6273(00)80943-5","article-title":"Intranuclear Inclusions of Expanded Polyglutamine Protein in Spinocerebellar Ataxia Type 3","volume":"19","author":"Paulson","year":"1997","journal-title":"Neuron"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9310","DOI":"10.1073\/pnas.152101299","article-title":"Live-cell imaging reveals divergent intracellular dynamics of polyglutamine disease proteins and supports a sequestration model of pathogenesis","volume":"99","author":"Chai","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s10059-013-0167-x","article-title":"Aggregation formation in the polyglutamine diseases: Protection at a cost?","volume":"36","author":"Todd","year":"2013","journal-title":"Mol. Cells"},{"key":"ref_12","first-page":"441","article-title":"Overexpression of Mutant Ataxin-3 in Mouse Cerebellum Induces Ataxia and Cerebellar Neuropathology","volume":"12","author":"Onofre","year":"2012","journal-title":"Cerebellum"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1002\/1873-3468.14298","article-title":"Mitochondria, energy, and metabolism in neuronal health and disease","volume":"596","author":"Trigo","year":"2022","journal-title":"FEBS Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrm3028","article-title":"Mechanisms of mitophagy","volume":"12","author":"Youle","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.1007\/s12035-020-01926-1","article-title":"The Role of Mitochondria in Neurodegenerative Diseases: The Lesson from Alzheimer\u2019s Disease and Parkinson\u2019s Disease","volume":"57","author":"Corti","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Morciano, G., Patergnani, S., Bonora, M., Pedriali, G., Tarocco, A., Bouhamida, E., Marchi, S., Ancora, G., Anania, G., and Wieckowski, M.R. (2020). Mitophagy in Cardiovascular Diseases. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030892"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e13327","DOI":"10.1111\/cpr.13327","article-title":"Mitophagy: A novel perspective for insighting into cancer and cancer treatment","volume":"55","author":"Song","year":"2022","journal-title":"Cell Prolif."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tang, S., Geng, Y., and Lin, Q. (2024). The role of mitophagy in metabolic diseases and its exercise intervention. Front. Physiol., 15.","DOI":"10.3389\/fphys.2024.1339128"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.nbd.2008.01.011","article-title":"Study of subcellular localization and proteolysis of ataxin-3","volume":"30","author":"Pozzi","year":"2008","journal-title":"Neurobiol. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.neuint.2017.10.013","article-title":"Mass spectrometry analyses of normal and polyglutamine expanded ataxin-3 reveal novel interaction partners involved in mitochondrial function","volume":"112","author":"Kristensen","year":"2018","journal-title":"Neurochem. Int."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wiatr, K., Marczak, \u0141., P\u00e9rot, J.B., Brouillet, E., Flament, J., and Figiel, M. (2021). Broad influence of mutant ataxin-3 on the proteome of the adult brain, young neurons, and axons reveals central molecular processes and biomarkers in SCA3\/MJD using knock-in mouse model. Front. Mol. Neurosci., 14.","DOI":"10.3389\/fnmol.2021.658339"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Almeida, F., Ferreira, I.L., Naia, L., Marinho, D., Vila\u00e7a-Ferreira, A.C., Costa, M.D., Duarte-Silva, S., Maciel, P., and Rego, A.C. (2023). Mitochondrial Dysfunction and Decreased Cytochrome c in Cell and Animal Models of Machado\u2013Joseph Disease. Cells, 12.","DOI":"10.3390\/cells12192397"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1159\/000339207","article-title":"Patterns of Mitochondrial DNA Damage in Blood and Brain Tissues of a Transgenic Mouse Model of Machado-Joseph Disease","volume":"11","author":"Kazachkova","year":"2013","journal-title":"Neurodegener. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s12031-014-0360-1","article-title":"Differential mtDNA Damage Patterns in a Transgenic Mouse Model of Machado\u2013Joseph Disease (MJD\/SCA3)","volume":"55","author":"Ramos","year":"2014","journal-title":"J. Mol. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1002\/jnr.22011","article-title":"Decreased antioxidant enzyme activity and increased mitochondrial DNA damage in cellular models of Machado-Joseph disease","volume":"87","author":"Yu","year":"2009","journal-title":"J. Neurosci. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.1016\/j.jmb.2019.10.015","article-title":"Ubiquitin and Receptor-Dependent Mitophagy Pathways and Their Implication in Neurodegeneration","volume":"432","author":"Fritsch","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1007\/s12035-016-9753-1","article-title":"Clearance of damaged mitochondria through PINK1 stabilization by JNK and ERK MAPK signaling in chlorpyrifos-treated neuroblastoma cells","volume":"54","author":"Park","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.4161\/auto.26550","article-title":"Regulation and function of mitophagy in development and cancer","volume":"9","author":"Lu","year":"2013","journal-title":"Autophagy"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1080\/15548627.2015.1009794","article-title":"USP8 and PARK2\/parkin-mediated mitophagy","volume":"11","author":"Durcan","year":"2015","journal-title":"Autophagy"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.tcb.2018.07.004","article-title":"No Parkin Zone: Mitophagy without Parkin","volume":"28","author":"Villa","year":"2018","journal-title":"Trends Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"eabo4457","DOI":"10.1126\/scisignal.abo4457","article-title":"Deciphering functional roles and interplay between Beclin1 and Beclin2 in autophagosome formation and mitophagy","volume":"16","author":"Quiles","year":"2023","journal-title":"Sci. Signal."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"10249","DOI":"10.1523\/JNEUROSCI.1917-11.2011","article-title":"Parkin interacts with Ambra1 to induce mitophagy","volume":"31","author":"Cornelissen","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/cdd.2014.139","article-title":"AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62\/SQSTM1","volume":"22","author":"Strappazzon","year":"2014","journal-title":"Cell Death Differ."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5227","DOI":"10.1093\/hmg\/ddu244","article-title":"The deubiquitinase USP15 antagonizes Parkin-mediated mitochondrial ubiquitination and mitophagy","volume":"23","author":"Cornelissen","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/nature13418","article-title":"The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy","volume":"510","author":"Bingol","year":"2014","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jb\/mvac092","article-title":"Ubiquitin-mediated mitochondrial regulation by MITOL\/MARCHF5 at a glance","volume":"173","author":"Nagashima","year":"2022","journal-title":"J. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.1016\/j.celrep.2018.05.015","article-title":"Sam50 Regulates PINK1-Parkin-Mediated Mitophagy by Controlling PINK1 Stability and Mitochondrial Morphology","volume":"23","author":"Jian","year":"2018","journal-title":"Cell Rep."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Abudu, Y.P., Shrestha, B.K., Zhang, W., Palara, A., Brenne, H.B., Larsen, K.B., Wolfson, D.L., Dumitriu, G., \u00d8ie, C.I., and Ahluwalia, B.S. (2021). SAMM50 acts with p62 in piecemeal basal- and OXPHOS-induced mitophagy of SAM and MICOS components. J. Cell Biol., 220.","DOI":"10.1083\/jcb.202009092"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1161\/CIRCHEARTFAILURE.114.001635","article-title":"Tumor Necrosis Factor Receptor\u2013Associated Factor 2 Mediates Mitochondrial Autophagy","volume":"8","author":"Yang","year":"2015","journal-title":"Circ. Hear. Fail."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/j.freeradbiomed.2023.09.036","article-title":"p53 contributes to cardiovascular diseases via mitochondria dysfunction: A new paradigm","volume":"208","author":"Wang","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.1038\/ncomms3308","article-title":"Cytosolic p53 inhibits Parkin-mediated mitophagy and promotes mitochondrial dysfunction in the mouse heart","volume":"4","author":"Hoshino","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Yu, S., Du, M., Yin, A., Mai, Z., Wang, Y., Zhao, M., Wang, X., and Chen, T. (2020). Bcl-xL inhibits PINK1\/Parkin-dependent mitophagy by preventing mitochondrial Parkin accumulation. Int. J. Biochem. Cell Biol., 122.","DOI":"10.1016\/j.biocel.2020.105720"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1016\/j.celrep.2017.08.087","article-title":"Parkin-Independent Mitophagy Controls Chemotherapeutic Response in Cancer Cells","volume":"20","author":"Villa","year":"2017","journal-title":"Cell Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3476","DOI":"10.1093\/hmg\/ddw189","article-title":"The PINK1, synphilin-1 and SIAH-1 complex constitutes a novel mitophagy pathway","volume":"25","author":"Szargel","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1091\/mbc.e12-08-0607","article-title":"Regulation of mitophagy by the Gp78 E3 ubiquitin ligase","volume":"24","author":"Fu","year":"2013","journal-title":"Mol. Biol. Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1002\/tox.23115","article-title":"The crosstalk between mitochondrial dysfunction and endoplasmic reticulum stress promoted ATF4-mediated mitophagy induced by hexavalent chromium","volume":"36","author":"Dlamini","year":"2021","journal-title":"Environ. Toxicol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/cdd.2010.142","article-title":"Parkin is transcriptionally regulated by ATF4: Evidence for an interconnection between mitochondrial stress and ER stress","volume":"18","author":"Bouman","year":"2010","journal-title":"Cell Death Differ."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1111\/jnc.13412","article-title":"Mitochondrial and lysosomal biogenesis are activated following PINK 1\/parkin-mediated mitophagy","volume":"136","author":"Ivankovic","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1083\/jcb.201501002","article-title":"MiT\/TFE transcription factors are activated during mitophagy downstream of Parkin and Atg5","volume":"210","author":"Nezich","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4525","DOI":"10.1111\/febs.14980","article-title":"E2F1 activates MFN2 expression by binding to the promoter and decreases mitochondrial fission and mitophagy in HeLa cells","volume":"286","author":"Bucha","year":"2019","journal-title":"FEBS J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4429","DOI":"10.1093\/hmg\/ddv179","article-title":"TBK1 controls autophagosomal engulfment of polyubiquitinated mitochondria through p62\/SQSTM1 phosphorylation","volume":"24","author":"Matsumoto","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1016\/j.molcel.2023.04.021","article-title":"Unconventional initiation of PINK1\/Parkin mitophagy by Optineurin","volume":"83","author":"Nguyen","year":"2023","journal-title":"Mol. Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1126\/science.1205405","article-title":"Phosphorylation of the Autophagy Receptor Optineurin Restricts Salmonella Growth","volume":"333","author":"Wild","year":"2011","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3404","DOI":"10.1016\/j.molcel.2023.08.021","article-title":"Mitochondrial degradation: Mitophagy and beyond","volume":"83","author":"Uoselis","year":"2023","journal-title":"Mol. Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e31326","DOI":"10.7554\/eLife.31326","article-title":"Endosomal Rab cycles regulate Parkin-mediated mitophagy","volume":"7","author":"Yamano","year":"2018","journal-title":"eLife"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Shafique, A., Brughera, M., Lualdi, M., and Alberio, T. (2023). The Role of Rab Proteins in Mitophagy: Insights into Neurodegenerative Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076268"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e01612","DOI":"10.7554\/eLife.01612","article-title":"Mitochondrial Rab GAPs govern autophagosome biogenesis during mitophagy","volume":"3","author":"Yamano","year":"2014","journal-title":"eLife"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Poole, L.P., Bock-Hughes, A., Berardi, D.E., and Macleod, K.F. (2021). ULK1 promotes mitophagy via phosphorylation and stabilization of BNIP3. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-00170-4"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/cdd.2009.16","article-title":"Role of BNIP3 and NIX in cell death, autophagy, and mitophagy","volume":"16","author":"Zhang","year":"2009","journal-title":"Cell Death Differ."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ding, W.-X., Ni, H.-M., Li, M., Liao, Y., Chen, X., Stolz, D.B., Dorn, G.W., and Yin, X.-M. (2010). Nix Is Critical to Two Distinct Phases of Mitophagy, Reactive Oxygen Species-mediated Autophagy Induction and Parkin-Ubiquitin-p62-mediated Mitochondrial Priming. J. Biol. Chem., 285.","DOI":"10.1074\/jbc.M110.119537"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Fu, Z.-J., Wang, Z.-Y., Xu, L., Chen, X.-H., Li, X.-X., Liao, W.-T., Ma, H.-K., Jiang, M.-D., Xu, T.-T., and Xu, J. (2020). HIF-1\u03b1-BNIP3-mediated mitophagy in tubular cells protects against renal ischemia\/reperfusion injury. Redox Biol., 36.","DOI":"10.1016\/j.redox.2020.101671"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3817","DOI":"10.1007\/s00018-021-03774-1","article-title":"Mitophagy in tumorigenesis and metastasis","volume":"78","author":"Poole","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"15975","DOI":"10.1523\/JNEUROSCI.2499-14.2014","article-title":"Poly(ADP-Ribose) Polymerase-1 Causes Mitochondrial Damage and Neuron Death Mediated by Bnip3","volume":"34","author":"Lu","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Li, K., Xia, X., and Tong, Y. (2024). Multiple roles of mitochondrial autophagy receptor FUNDC1 in mitochondrial events and kidney disease. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1453365"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1080\/15548627.2016.1151580","article-title":"Mitophagy receptor FUNDC1 regulates mitochondrial dynamics and mitophagy","volume":"12","author":"Chen","year":"2016","journal-title":"Autophagy"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3755","DOI":"10.1038\/s41467-018-05722-3","article-title":"HUWE1 E3 ligase promotes PINK1\/PARKIN-independent mitophagy by regulating AMBRA1 activation via IKK\u03b1","volume":"9","author":"Peschiaroli","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"947","DOI":"10.15252\/embr.201643147","article-title":"FKBP8 recruits LC3A to mediate Parkin-independent mitophagy","volume":"18","author":"Bhujabal","year":"2017","journal-title":"Embo Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1080\/15548627.2015.1084459","article-title":"BCL2L13 is a mammalian homolog of the yeast mitophagy receptor Atg32","volume":"11","author":"Otsu","year":"2015","journal-title":"Autophagy"},{"key":"ref_69","first-page":"24","article-title":"Regulation of PRKN-independent mitophagy","volume":"18","author":"Lapao","year":"2021","journal-title":"Autophagy"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.molcel.2017.10.029","article-title":"Autophagosomal Content Profiling Reveals an LC3C-Dependent Piecemeal Mitophagy Pathway","volume":"68","author":"Eck","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/cr.2017.23","article-title":"PHB2\/prohibitin 2: An inner membrane mitophagy receptor","volume":"27","author":"Lahiri","year":"2017","journal-title":"Cell Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.cell.2016.11.042","article-title":"Prohibitin 2 Is an Inner Mitochondrial Membrane Mitophagy Receptor","volume":"168","author":"Wei","year":"2017","journal-title":"Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"12646","DOI":"10.1038\/ncomms12646","article-title":"VCP recruitment to mitochondria causes mitophagy impairment and neurodegeneration in models of Huntington\u2019s disease","volume":"7","author":"Guo","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"114323","DOI":"10.1016\/j.yexcr.2024.114323","article-title":"NLRX1 and STING alleviate renal ischemia-reperfusion injury by regulating LC3 lipidation during mitophagy","volume":"443","author":"Liao","year":"2024","journal-title":"Exp. Cell Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1038\/onc.2011.35","article-title":"The pro-longevity gene FoxO3 is a direct target of the p53 tumor suppressor","volume":"30","author":"Renault","year":"2011","journal-title":"Oncogene"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1093\/hmg\/ddq452","article-title":"The Machado\u2013Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability","volume":"20","author":"Durcan","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Harmuth, T., Weber, J.J., Zimmer, A.J., Sowa, A.S., Schmidt, J., Fitzgerald, J.C., Sch\u00f6ls, L., Riess, O., and H\u00fcbener-Schmid, J. (2022). Mitochondrial Dysfunction in Spinocerebellar Ataxia Type 3 Is Linked to VDAC1 Deubiquitination. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23115933"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.nbd.2005.07.011","article-title":"Polyglutamine-expanded ataxin-3 activates mitochondrial apoptotic pathway by upregulating Bax and downregulating Bcl-xL","volume":"21","author":"Chou","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1101\/gad.949602","article-title":"TRAIL-induced apoptosis requires Bax-dependent mitochondrial release of Smac\/DIABLO","volume":"16","author":"Deng","year":"2002","journal-title":"Genes Dev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"11345","DOI":"10.1074\/jbc.M109893200","article-title":"Bcl-2 and Bcl-xL inhibit CD95-mediated apoptosis by preventing mitochondrial release of Smac\/DIABLO and subsequent inactivation of X-linked inhibitor-of-apoptosis protein","volume":"277","author":"Sun","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4268","DOI":"10.1093\/hmg\/ddp380","article-title":"Gp78, an ER associated E3, promotes SOD1 and ataxin-3 degradation","volume":"18","author":"Ying","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1038\/sj.emboj.7601043","article-title":"An arginine\/lysine-rich motif is crucial for VCP\/p97-mediated modulation of ataxin-3 fibrillogenesis","volume":"25","author":"Boeddrich","year":"2006","journal-title":"EMBO J."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"La\u00e7o, M.N., Cortes, L., Travis, S.M., Paulson, H.L., and Rego, A.C. (2012). Valosin-Containing Protein (VCP\/p97) Is an Activator of Wild-Type Ataxin-3. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043563"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/s41589-020-00726-x","article-title":"VCP\/p97 regulates Beclin-1-dependent autophagy initiation","volume":"17","author":"Hill","year":"2021","journal-title":"Nat. Chem. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1093\/brain\/awr047","article-title":"Overexpression of the autophagic beclin-1 protein clears mutant ataxin-3 and alleviates Machado\u2013Joseph disease","volume":"134","author":"Auregan","year":"2011","journal-title":"Brain"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nature22078","article-title":"Polyglutamine tracts regulate beclin 1-dependent autophagy","volume":"545","author":"Ashkenazi","year":"2017","journal-title":"Nature"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Chapman, T.P., Corridoni, D., Shiraishi, S., Pandey, S., Aulicino, A., Wigfield, S., Costa, M.D.C., Th\u00e9z\u00e9nas, M.-L., Paulson, H., and Fischer, R. (2019). Ataxin-3 Links NOD2 and TLR2 Mediated Innate Immune Sensing and Metabolism in Myeloid Cells. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01495"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"105920","DOI":"10.1016\/j.isci.2022.105920","article-title":"How good are AlphaFold models for docking-based virtual screening?","volume":"26","author":"Scardino","year":"2023","journal-title":"Iscience"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Sousa, A., Rocha, S., Vieira, J., Reboiro-Jato, M., L\u00f3pez-Fern\u00e1ndez, H., and Vieira, C.P. (2023). On the identification of potential novel therapeutic targets for spinocerebellar ataxia type 1 (SCA1) neurodegenerative disease using EvoPPI3. J. Integr. Bioinform., 20.","DOI":"10.1515\/jib-2022-0056"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1038\/s41596-022-00728-0","article-title":"I-TASSER-MTD: A deep-learning-based platform for multi-domain protein structure and function prediction","volume":"17","author":"Zhou","year":"2022","journal-title":"Nat. Protoc."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Tang, T., Zhang, X., Liu, Y., Peng, H., Zheng, B., Yin, Y., and Zeng, X. (2023). Machine learning on protein\u2013protein interaction prediction: Models, challenges and trends. Brief. Bioinform., 24.","DOI":"10.1093\/bib\/bbad076"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1146\/annurev-biodatasci-011720-104428","article-title":"Protein-Protein Interaction Methods and Protein Phase Separation","volume":"3","author":"Savojardo","year":"2020","journal-title":"Annu. Rev. Biomed. Data Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"i343","DOI":"10.1093\/bioinformatics\/btz324","article-title":"SCRIBER: Accurate and partner type-specific prediction of protein-binding residues from proteins sequences","volume":"35","author":"Zhang","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1093\/bioinformatics\/btq302","article-title":"Applying the Na\u00efve Bayes classifier with kernel density estimation to the prediction of protein\u2013protein interaction sites","volume":"26","author":"Murakami","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1021\/ja026939x","article-title":"HADDOCK: A Protein\u2212Protein Docking Approach Based on Biochemical or Biophysical Information","volume":"125","author":"Dominguez","year":"2003","journal-title":"J. Am. Chem. Soc."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.jmb.2007.05.022","article-title":"Inference of Macromolecular Assemblies from Crystalline State","volume":"372","author":"Krissinel","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00401-012-1000-x","article-title":"Brain pathology of spinocerebellar ataxias","volume":"124","author":"Seidel","year":"2012","journal-title":"Acta Neuropathol."},{"key":"ref_98","first-page":"798","article-title":"Protein\u2013protein interactions: Detection, reliability assessment and applications","volume":"18","author":"Peng","year":"2017","journal-title":"Brief. Bioinform."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1002\/pro.3859","article-title":"The metastable states of proteins","volume":"29","author":"Ghosh","year":"2020","journal-title":"Protein Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/sj.emboj.7600081","article-title":"Molecular clearance of ataxin-3 is regulated by a mammalian E4","volume":"23","author":"Matsumoto","year":"2004","journal-title":"EMBO J."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.4161\/auto.25884","article-title":"The TOMM machinery is a molecular switch in PINK1 and PARK2\/PARKIN-dependent mitochondrial clearance","volume":"9","author":"Bertolin","year":"2013","journal-title":"Autophagy"},{"key":"ref_102","first-page":"18","article-title":"A Molecular Approach to Mitophagy and Mitochondrial Dynamics","volume":"41","author":"Yoo","year":"2018","journal-title":"Mol. Cells"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e167728","DOI":"10.1172\/JCI167728","article-title":"CRISPR screening identifies the deubiquitylase ATXN3 as a PD-L1\u2013positive regulator for tumor immune evasion","volume":"133","author":"Wang","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Fern\u00e1ndez, H., Ferreira, P., Reboiro-Jato, M., Vieira, C.P., and Vieira, J. (2022). The pegi3s bioinformatics docker images project. Practical Applications of Computational Biology & Bioinformatics, 15th International Conference (PACBB 2021), Springer.","DOI":"10.1007\/978-3-030-86258-9_4"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1325\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:26:48Z","timestamp":1760027208000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1325"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,4]]},"references-count":104,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["ijms26031325"],"URL":"https:\/\/doi.org\/10.3390\/ijms26031325","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,4]]}}}