Characterisation of a C elegans strain presenting with a mitochondrial contact site and cristae organizing system (MICOS) subunit deficiency

Abstract

Mitochondrial architecture varies remarkably from one tissue to another, and aberrations in mitochondrial architecture are associated with several dysfunctions. This indicates that mitochondrial function and architecture are intertwined. Existing literature has contributed significantly to our current understanding of the role mitochondria play in ATP production, and apoptosis. However, our understanding of how mitochondria attain their definite shape to perform their routine functions is less clear. The inner mitochondrial morphology is characterized by cristae which undergo membrane bending at cristae junctions. The cristae can be lamellar, tubular, or triangular in astrocytes. Moreover, cristae structure is associated directly with mitochondrial function. High energy-demanding tissues such as neurons and skeletal muscles show mainly lamellar cristae, suggesting a large planer membrane area is essential to accommodate the respiratory chain complexes. While the mitochondrial contact site and cristae organizing system (MICOS) plays a critical role in the formation of cristae, the mechanism of cristae formation is a sophisticated process that has not yet been fully elucidated. The aim of this study was to characterize a Caenorhabditis elegans (C. elegans) strain presenting with a MICOS subunit (Mic27) deficiency. The mutant C. elegans strain (VC1196) harbours a mutation in moma-1 gene which is an ortholog of mammalian APOOL. Existing literature suggests that coordination of the MICOS complex with respiratory complexes and lipids establishes the inner membrane architecture as an assembly of Mic27 and Mic10 is highly dependent on mitochondrial lipid cardiolipin and respiratory complexes. Thus, the results obtained in this study support the initially stated hypothesis as the VC1196 knockout deficient in the MICOS subunit showed aberrant cristae morphology, decreased mitochondrial oxidative phosphorylation (OXPHOS) enzyme activity and, respiration as well as poor scores in phenotypic assays. The pronounced disease phenotype in the VC1196 strain re-ported in this study illustrated its usefulness as a mitochondrial disease model for future studies in this field.