biostudies-literatureUnknown8(29)Paradis MDynamic contacts are formed between endoplasmic reticulum (ER) and mitochondria that enable the exchange of calcium and phospholipids. Disturbed contacts between ER and mitochondria impair mitochondrial dynamics and are a molecular hallmark of Parkinson's disease, which is also characterized by impaired complex I activity and dopaminergic neuron degeneration. Here, we analyzed the role of cysteine-rich with EGF-like domain (Creld), a poorly characterized risk gene for Parkinson's disease, in the regulation of mitochondrial dynamics and function. We found that loss of Creld leads to mitochondrial hyperfusion and reduced ROS signaling in <i>Drosophila melanogaster</i>, <i>Xenopus tropicalis</i>, and human cells. Creld fly mutants show differences in ER-mitochondria contacts and reduced respiScience advanceseabo0155https://www.ebi.ac.uk/biostudies/studies/S-EPMC9307246biostudies-literatureThe ER protein Creld regulates ER-mitochondria contact dynamics and respiratory complex 1 activity.PMC9307246Meyer CPaululat AJamitzky ISellin JParadis MKucharowski NKalinowski JBauer RThiele CMaya Palacios SJEdwards Faret GStumpges BBulow MHfalseThe ER protein Creld regulates ER-mitochondria contact dynamics and respiratory complex 1 activity.Dynamic contacts are formed between endoplasmic reticulum (ER) and mitochondria that enable the exchange of calcium and phospholipids. Disturbed contacts between ER and mitochondria impair mitochondrial dynamics and are a molecular hallmark of Parkinson's disease, which is also characterized by impaired complex I activity and dopaminergic neuron degeneration. Here, we analyzed the role of cysteine-rich with EGF-like domain (Creld), a poorly characterized risk gene for Parkinson's disease, in the regulation of mitochondrial dynamics and function. We found that loss of Creld leads to mitochondrial hyperfusion and reduced ROS signaling in <i>Drosophila melanogaster</i>, <i>Xenopus tropicalis</i>, and human cells. Creld fly mutants show differences in ER-mitochondria contacts and reduced respi2022-01-01T00:00:00Z2022 Jul2025-04-22T11:28:21.31Z2025-04-05T23:59:48.261ZS-EPMC93072463586779510.1126/sciadv.abo0155