Sandoval Hector, Yao Chi-Kuang, Chen Kuchuan, Jaiswal Manish, Donti Taraka, Lin Yong Qi, Bayat Vafa, Xiong Bo, Zhang Ke, David Gabriela, Charng Wu-Lin, Yamamoto Shinya, Duraine Lita, Graham Brett H, Bellen Hugo J
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
Program in Developmental Biology, Baylor College of Medicine, Houston, United States.
Elife. 2014 Oct 14;3:e03558. doi: 10.7554/eLife.03558.
Mitochondrial fusion and fission affect the distribution and quality control of mitochondria. We show that Marf (Mitochondrial associated regulatory factor), is required for mitochondrial fusion and transport in long axons. Moreover, loss of Marf leads to a severe depletion of mitochondria in neuromuscular junctions (NMJs). Marf mutants also fail to maintain proper synaptic transmission at NMJs upon repetitive stimulation, similar to Drp1 fission mutants. However, unlike Drp1, loss of Marf leads to NMJ morphology defects and extended larval lifespan. Marf is required to form contacts between the endoplasmic reticulum and/or lipid droplets (LDs) and for proper storage of cholesterol and ecdysone synthesis in ring glands. Interestingly, human Mitofusin-2 rescues the loss of LD but both Mitofusin-1 and Mitofusin-2 are required for steroid-hormone synthesis. Our data show that Marf and Mitofusins share an evolutionarily conserved role in mitochondrial transport, cholesterol ester storage and steroid-hormone synthesis.
线粒体融合与裂变影响线粒体的分布和质量控制。我们发现，Marf（线粒体相关调节因子）是长轴突中线粒体融合与运输所必需的。此外，Marf的缺失会导致神经肌肉接头（NMJ）中线粒体严重耗竭。与Drp1裂变突变体类似，Marf突变体在重复刺激时也无法维持NMJ处的正常突触传递。然而，与Drp1不同的是，Marf的缺失会导致NMJ形态缺陷并延长幼虫寿命。Marf是在内质网和/或脂滴（LD）之间形成接触以及在环腺中正确储存胆固醇和蜕皮激素合成所必需的。有趣的是，人类线粒体融合蛋白2能挽救脂滴的缺失，但类固醇激素合成需要线粒体融合蛋白1和线粒体融合蛋白2。我们的数据表明，Marf和线粒体融合蛋白在线粒体运输、胆固醇酯储存和类固醇激素合成中具有进化上保守的作用。
