Elucidation of the role of the MICOS complex in signal transduction from mitocondrial DNA nucleoids

Abstract: The MICOS complex protein MicF has recently been identified to play a vital role in the mitochondrial DNA inheritance checkpoint, a control system that halts cell cycle progression in cells lacking mitochondrial DNA (mtDNA). We show in this report that another member of the complex, MicA, also plays an important role in the mtDNA inheritance checkpoint as its deletion led to cell cycle progression in cells lacking mtDNA (Rho0 cells). We observed that deletion of MicA, just like deletion of MicF, led to aggregated mtDNA in addition to the severe defects in the architecture of the inner mitochondrial membrane observed in all MICOS deletion strains. These findings lead us to believe that MicA and MicF might be involved in the signal transduction from mtDNA across the mitochondrial membranes and that their deletion leads to loss of contact sites between the membranes and thereby renders transduction across the membranes impossible.