Abstract
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.
Highlights
Mitochondrial dynamics plays a critical role in the control of organelle shape, size, number, function and quality control of mitochondria from yeast to mammals (Westermann, 2009; Chan, 2012)
Mitofusin 1 (Mfn1) and Mitofusin 2 (Mfn2) regulate outer mitochondrial fusion whereas inner membrane fusion is controlled by Optic atrophy protein 1 (Opa1)
We find that ring glands (RG) specific expression of human MFN2 restores the proper number of lipid droplets (LDs) levels and organelle contacts in Marf mutants whereas expression of human MFN1 (Dorn et al, 2011) does not (Figure 7A,C and Figure 7—figure supplement 1), indicating that MFN2 can rescue the defect in LD synthesis
Summary
Mitochondrial dynamics plays a critical role in the control of organelle shape, size, number, function and quality control of mitochondria from yeast to mammals (Westermann, 2009; Chan, 2012). It consists of fusion and fission of mitochondria, which are regulated by several GTPases (van der Bliek et al, 2013). Mitochondrial fusion requires the fusion of the outer membrane followed by inner membrane fusion (Chan, 2012; Mishra et al, 2014). Mitofusin 1 (Mfn1) and Mitofusin 2 (Mfn2) regulate outer mitochondrial fusion whereas inner membrane fusion is controlled by Optic atrophy protein 1 (Opa). Decreased fusion results in fragmented round mitochondria, while defective fission leads to fused and enlarged mitochondria (van der Bliek et al, 2013)
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