Phospholipids can regulate complex I assembly independent of their role in maintaining mitochondrial membrane integrity.

Anjaneyulu Murari, Shauna-Kay Rhooms, Divya Vimal, Kaniz Fatima Binte Hossain, Sanjay Saini, Maximino Villanueva, Michael Schlame, Edward Owusu-Ansah

Cell reports 2023 Aug 29

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Several phospholipid (PL) molecules are intertwined with some mitochondrial complex I (CI) subunits in the membrane domain of CI, but their function is unclear. We report that when the Drosophila melanogaster ortholog of the intramitochondrial PL transporter, STARD7, is severely disrupted, assembly of the oxidative phosphorylation (OXPHOS) system is impaired, and the biogenesis of several CI subcomplexes is hampered. However, intriguingly, a restrained knockdown of STARD7 impairs the incorporation of NDUFS5 and NDUFA1 into the proximal part of the CI membrane domain without directly affecting the incorporation of subunits in the distal part of the membrane domain, OXPHOS complexes already assembled, or mitochondrial cristae integrity. Importantly, the restrained knockdown of STARD7 appears to induce a modest amount of cardiolipin remodeling, indicating that there could be some alteration in the composition of the mitochondrial phospholipidome. We conclude that PLs can regulate CI biogenesis independent of their role in maintaining mitochondrial membrane integrity. Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Anjaneyulu Murari, Shauna-Kay Rhooms, Divya Vimal, Kaniz Fatima Binte Hossain, Sanjay Saini, Maximino Villanueva, Michael Schlame, Edward Owusu-Ansah. Phospholipids can regulate complex I assembly independent of their role in maintaining mitochondrial membrane integrity. Cell reports. 2023 Aug 29;42(8):112846