Uncoupling the Dynamics of Inner and Outer Mitochondrial Membrane Fission

Mitochondria are dynamic organelles undergoing constant changes in their morphology through two opposing processes; mitochondrial fission and fusion. The current model of mitochondria fission begins with the endoplasmic reticulum (ER) localizing to the mitochondrial outer membrane and initiating membrane constriction. Additional key molecular players, specifically a mitochondrial transmembrane protein, MFF and a cytosolic GTPase, Drp1, localize to the outer mitochondrial membrane to drive constriction and subsequent fission of the mitochondria. While several proteins have been identified to be involved in mitochondrial fission, almost all of them function at the outer mitochondrial membrane (OMM). We therefore have very little knowledge about what regulates the fission of the inner mitochondrial membrane (IMM). Using live cell fluorescent microscopy, we have quantitatively assessed the morphological state of the IMM and OMM leading up to mitochondrial fission. Our results show that IMM constriction is an early event in mitochondrial fission, often preceding OMM constriction. Furthermore, we show that IMM constriction is independent of Drp1, as membrane constriction is still prevalent even in the absence of Drp1. Together our data suggests that IMM and OMM constriction are separate events and the mechanisms driving constriction of both membranes may be independent of each other