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

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 or-tholog 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 cardio-lipin remodeling, indicating that there could be some alteration in the composition of the mitochondrial phos-pholipidome. We conclude that PLs can regulate CI biogenesis independent of their role in maintaining mito-chondrial membrane integrity.

Automated summary

The function of phospholipids intertwined with mitochondrial complex I subunits in the membrane domain of CI is unclear. However, disrupted PL transporter STARD7 impairs assembly of OXPHOS system and CI subcomplexes, while restrained knockdown of STARD7 affects incorporation of NDUFS5 and NDUFA1 into the proximal part of CI membrane domain. The knockdown also induces modest cardio-lipin remodeling, indicating alteration in mitochondrial phospholipid composition.