Abstract
ABSTRACTThe mitochondrial contact site and cristae organizing system (MICOS) is a multi-protein interaction hub that helps define mitochondrial ultrastructure. While the functional importance of MICOS is mostly characterized in yeast and mammalian cells in culture, the contributions of MICOS to tissue homeostasis in vivo remain further elucidation. In this study, we examined how knocking down expression of Drosophila MICOS genes affects mitochondrial function and muscle tissue homeostasis. We found that CG5903/MIC26-MIC27 colocalizes and functions with Mitofilin/MIC60 and QIL1/MIC13 as a Drosophila MICOS component; knocking down expression of any of these three genes predictably altered mitochondrial morphology, causing loss of cristae junctions, and disruption of cristae packing. Furthermore, the knockdown flies exhibited low mitochondrial membrane potential, fusion/fission imbalances, increased mitophagy, and limited cell death. Reductions in climbing ability indicated deficits in muscle function. Knocking down MICOS genes also caused reduced mtDNA content and fragmented mitochondrial nucleoid structure in Drosophila. Together, our data demonstrate an essential role of Drosophila MICOS in maintaining proper homeostasis of mitochondrial structure and function to promote the function of muscle tissue.
Highlights
Mitochondria have a unique architecture that is required for essential cellular processes (Cogliati et al, 2016; Mannella, 2006; Zick et al, 2009)
We found that knocking down CG5903/MIC26-MIC27 caused flight muscle phenotypes similar to those seen in Mitofilin/MIC60and QIL1/MIC13-knockdown flies, including altered cristae morphology, reduced membrane potential, and increased mitochondrial network fragmentation
Knockdown of CG5903/MIC26-MIC27, Mitofilin/MIC60, or QIL1/MIC13 perturbs mitochondrial structure, membrane potential, and the mitochondrial network in Drosophila muscle tissue To explore how mitochondrial contact site and cristae organizing system (MICOS) influences mitochondria and tissue function, we examined the phenotypes of CG5903/MIC26-MIC27, Mitofilin/ MIC60, and QIL1/MIC13-knockdown flies
Summary
Mitochondria have a unique architecture that is required for essential cellular processes (Cogliati et al, 2016; Mannella, 2006; Zick et al, 2009). The cristae harbor electron transport chain (ETC) assemblies that generate the proton gradient and membrane potential required for ATP production. Structural alterations in the cristae are often associated with mitochondrial dysfunction (Cogliati et al, 2016; Mannella, 2006; Zick et al, 2009). Cristae contact the IBM at cristae junctions, which require the mitochondrial contact site and cristae organizing system (MICOS) for their formation and maintenance (Harner et al, 2011; von der Malsburg et al, 2011)
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