{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:51:12Z","timestamp":1791805872198,"version":"4.3.4"},"posted":{"date-parts":[[2026,7,29]]},"group-title":"Neuroscience","reference-count":58,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH\/NINDS"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Tubulin polymerization promoting proteins (TPPPs) are known for their cytoskeletal regulation across species; however, emerging evidence suggests broader cellular functions, including potential roles in mitochondrial biology. Here, we identify the\n                  <jats:italic>Drosophila<\/jats:italic>\n                  homolog of human TPPP, Ringer, as a previously unrecognized regulator of mitochondrial bioenergetics and electron transport chain Complex I (CI) function. Ringer is enriched in the mitochondrial matrix, and its loss results in reduced levels of multiple CI subunits and assembly factors and a significant decrease in CI enzymatic activity. Notably, in addition to TPPP dysfunction, similar deficits are observed in postmortem human Parkinson\u2019s disease (PD) brain tissues, underscoring the translational relevance of our\n                  <jats:italic>Drosophila<\/jats:italic>\n                  model. Pharmacological administration of resveratrol, a reactive oxygen species (ROS) scavenger, reduces mitochondrial superoxide levels and improves CI enzymatic activity and ATP production in\n                  <jats:italic>ringer<\/jats:italic>\n                  mutants, demonstrating that targeted antioxidant therapeutics can improve bioenergetic functions in\n                  <jats:italic>ringer<\/jats:italic>\n                  mutants. Together, these findings establish Ringer as a key regulator of mitochondrial bioenergetics and reveal Ringer-induced CI dysfunction as a phenotype relevant to mitochondrial abnormalities observed in PD, and provide a robust and translationally meaningful framework for investigating mitochondrial dysfunction in PD.\n                <\/jats:p>","DOI":"10.64898\/2026.07.27.741040","type":"posted-content","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:30:35Z","timestamp":1785321035000},"source":"Crossref","is-referenced-by-count":0,"title":["Ringer Loss in\n                  <i>Drosophila<\/i>\n                  Uncovers Mitochondrial Complex I Deficits Relevant to Human Parkinson\u2019s Disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8131-173X","authenticated-orcid":false,"given":"Haven G.","family":"Tillmon","sequence":"first","affiliation":[{"name":"Department of Cellular and Integrative Physiology, University of Texas Health Science Center San Antonio, Joe R. and Teresa Lozano Long School of Medicine, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savannah K.","family":"Boyen","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, University of Texas Health Science Center San Antonio, Joe R. and Teresa Lozano Long School of Medicine, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Velazquez","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, University of Texas Health Science Center San Antonio, Joe R. and Teresa Lozano Long School of Medicine, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle E.","family":"Urbina-Berlanga","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, University of Texas Health Science Center San Antonio, Joe R. and Teresa Lozano Long School of Medicine, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Sciortino","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, University of Texas Health Science Center San Antonio, Joe R. and Teresa Lozano Long School of Medicine, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, University of Texas Health Science Center San Antonio, Joe R. and Teresa Lozano Long School of Medicine, San Antonio, Texas, USA"},{"name":"Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, Joe R. and Teresa Lozano Long School of Medicine, San Antonio, Texas, USA"},{"name":"Perry and Ruby Stevens Parkinson\u2019s Disease Center of Excellence, University of Texas Health Science Center, San Antonio, Joe R. and Teresa Lozano Long School of Medicine, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026101204400550000_2026.07.27.741040v2.1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2436331100"},{"key":"2026101204400550000_2026.07.27.741040v2.2","doi-asserted-by":"publisher","DOI":"10.1021\/bi061305e"},{"key":"2026101204400550000_2026.07.27.741040v2.3","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.187294"},{"key":"2026101204400550000_2026.07.27.741040v2.4","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00192"},{"key":"2026101204400550000_2026.07.27.741040v2.5","doi-asserted-by":"crossref","unstructured":"Ota, K. et al. 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