Phospholipids can regulate complex I assembly independent of their role in maintaining mitochondrial membrane integrity.
Phospholipids can regulate complex I assembly independent of their role in maintaining mitochondrial membrane integrity.
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DOI：
10.1016/j.celrep.2023.112846
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发表时间：
2023-08-29
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
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一些磷脂（PL）分子与线粒体复合体I （CI）亚基在CI的膜结构域中交织在一起，但其功能尚不清楚。我们报道，当果蝇线粒体内PL转运体STARD7的同源物被严重破坏时，氧化磷酸化（OXPHOS）系统的组装受到损害，并且几个CI亚复合物的生物发生受到阻碍。然而，有趣的是，抑制STARD7的下调会损害NDUFS5和NDUFA1在CI膜结构域近端部分的结合，而不会直接影响亚基在膜结构域远端部分的结合、已经组装的OXPHOS复合物或线粒体嵴的完整性。重要的是，STARD7的抑制下调似乎诱导了适量的心磷脂重塑，这表明线粒体磷脂组的组成可能发生了一些改变。我们得出结论，PLs可以独立于维持线粒体膜完整性的作用来调节CI的生物发生。Murari等人的研究表明，果蝇（Drosophila melanogaster）飞行肌中磷脂转运体STARD7的抑制失活可以在不改变线粒体膜完整性的情况下损害复合物I生物发生的特定步骤，这提高了STARD7点突变可能导致某些复合物I疾病的可能性。
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. Murari et al. show that a restrained inactivation of the phospholipid transporter, STARD7, in fruit fly (Drosophila melanogaster) flight muscles can impair specific steps in the biogenesis of complex I without altering mitochondrial membrane integrity, raising the possibility that point mutations in STARD7 could cause some complex I disorders.
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影响因子：
64.8
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1126/stke.2202004pl6
发表时间：
2004-02-12
期刊：
Science's STKE : signal transduction knowledge environment
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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