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

ABSTRACT: 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 phospholipid transporter, STARD7, is severely disrupted, assembly of the oxidative phosphorylation (OXPHOS) system is impaired and 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 appeared to induce a modest amount of cardiolipin remodeling, indicating that there could be some alteration of the composition of the mitochondrial phospholipidome. We conclude that PLs can regulate CI biogenesis independent of their role in maintaining mitochondrial membrane integrity.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Drosophila Melanogaster (ncbitaxon:7227)

SUBMITTER: Dr. Edward Owusu-Ansah Dr. Michael Schlame

PROVIDER: MSV000092254 | MassIVE | Fri Jun 23 13:17:00 BST 2023

REPOSITORIES: MassIVE

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

Project description: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 phospholipid transporter, STARD7, is severely disrupted, assembly of the oxidative phosphorylation (OXPHOS) system is impaired and 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 appeared to induce a modest amount of cardiolipin remodeling, indicating that there could be some alteration of the composition of the mitochondrial phospholipidome. We conclude that PLs can regulate CI biogenesis independent of their role in maintaining mitochondrial membrane integrity.

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