{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T16:03:46Z","timestamp":1771517026905,"version":"3.50.1"},"reference-count":57,"publisher":"The Company of Biologists","issue":"1","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005879","name":"National Centre for Biological Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005879","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Our understanding of mechanisms underlying familial Parkinson's disease (PD) have benefitted from studies in Drosophila models of PD. However, in a majority of patients with PD, the disease occurs sporadically, and cellular phenotypes that arise early in sporadic PD are not yet fully understood. A genetic predisposition, arising from variants in pathways that impact dopaminergic neuron health could be one cause of sporadic PD. Here, we studied Drosophila with single-copy mutation of the recessive IP3R-encoding gene (itpr) in combination with a recessive null mutation of the parkin gene. Whereas individual mutants appeared normal, in combination, the genes synergised so that flies exhibited flight motor deficits with a focus in a subset of central dopaminergic neurons. Surprisingly, mitophagy and mitochondrial Ca2+ were barely affected. Instead, flight motor deficits correlated with elevated levels of mitochondrial H2O2, and reducing H2O2 levels by genetic means restored mitochondrial function and flight to a significant extent. This study underlines the importance of mitochondrial oxidative stress as an early phenotype in PD and suggests that humans with recessive variants in either pathway have a higher chance of developing sporadic PD.<\/jats:p>","DOI":"10.1242\/dmm.052146","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T13:18:31Z","timestamp":1763126311000},"source":"Crossref","is-referenced-by-count":2,"title":["Synergism of IP3R and Parkin mutants identifies mitochondrial stress as an early feature of Parkinson's disease"],"prefix":"10.1242","volume":"19","author":[{"given":"Mrudula","family":"Dileep","sequence":"first","affiliation":[{"name":"National Centre for Biological Sciences, TIFR 1 , Bengaluru 560065 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anamika","family":"Sharma","sequence":"additional","affiliation":[{"name":"National Centre for Biological Sciences, TIFR 1 , Bengaluru 560065 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nandashree","family":"Kasturacharya","sequence":"additional","affiliation":[{"name":"National Centre for Biological Sciences, TIFR 1 , Bengaluru 560065 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed Kavish","family":"Nizami","sequence":"additional","affiliation":[{"name":"National Centre for Biological Sciences, TIFR 1 , Bengaluru 560065 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steffy B.","family":"Manjila","sequence":"additional","affiliation":[{"name":"National Centre for Biological Sciences, TIFR 1 , Bengaluru 560065 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashita","family":"Bhan","sequence":"additional","affiliation":[{"name":"National Centre for Biological Sciences, TIFR 1 , Bengaluru 560065 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7194-383X","authenticated-orcid":false,"given":"Gaiti","family":"Hasan","sequence":"additional","affiliation":[{"name":"National Centre for Biological Sciences, TIFR 1 , Bengaluru 560065 ,","place":["India"]},{"name":"Centre for High Impact Neuroscience and Translational Applications (CHINTA), TCG-Crest 2 , Kolkata 700091 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"2026021910013461700_DMM052146C1","doi-asserted-by":"publisher","first-page":"3922","DOI":"10.1038\/s41598-022-07909-7","article-title":"An assessment of the rescue action of resveratrol in parkin loss of function-induced oxidative stress in Drosophila melanogaster","volume":"12","author":"Adedara","year":"2022","journal-title":"Sci. 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