Abstract

Defects in OXPHOS is a major cause of mitochondrial disease with defects in the first enzyme, complex I, being a major contributor to disease. Complex I is composed of 45 subunits in humans, making it one of the largest known multi-subunit membrane protein complexes. The enzyme is assembled via a series of intermediate modules involving the dynamic interplay between a suite of assembly factors. The dynamic nature of mitochondria is also linked to metabolic and disease states, stress and quality control. Fission and fusion is co-ordinated by a group of dynamin family GTPases. Mitochondrial fission is executed by dynamin related protein 1 (Drp1) which is recruited to the outer membrane by adaptor proteins Mff and MiD49/51. Other players involved in fission include mitochondrial constriction machineries involving the ER, actin and other dynamins. The machineries involved in complex I assembly and mitochondrial fission will be outlined.