Dynamic Coordination of Mitochondrial Structure and Function
  • Woong Sun Ph.D
  • SLS Colloquia / Nov 1st 04:00 pm / BLDG 110 Room N104
Abstract

Mitochondria have functionally and structurally distinct outer- (OMM) and inner-membranes (IMM). Thus, mitochondrial morphology is controlled by independent but coordinated activity of fission and fusion of two membranes by the endocytosis-like machineries, which include dynamin-related protein 1 (Drp1). Mitochondrial fission is also implicated in the mitophagy, a mitochondrial quality control process for eliminating dysfunctional mitochondria whose mitochondrial membrane potential (MMP) is diminished. However, the coordination between the function (i.e. MMP) and structure (i.e. fission) of mitochondria is poorly understood. Because mitochondrial physiology, including oxidative phosphorylation, is primarily linked to the IMM, we focused on the morphological alterations of the IMM, and discovered that spontaneous and repetitive Constriction of Mitochondrial Inner Compartment (CoMIC) associated with subsequent division in neurons. CoMIC is mediated by intra-mitochondrial influx of Ca2+ and MMP-dependent activation of optic atrophy 1 (Opa1). On the other hand, Drp1 at the OMM also interacts with mitochondrial zinc transporter Zip1 and promotes Zn2+ entry through the Zip1-MCU complex, leading to the MMP reduction. After division, healthy mitochondria restore MMP levels and participate in the fusion-fission cycle again, but mitochondria that fail to restore MMP undergo mitophagy. Thus, interfering with the interaction between Drp1 and Zip1 blocks the reduction of MMP and the subsequent mitophagic selection of damaged mitochondria. These results suggest that Drp1 plays an essential role in linking mitochondrial structure and function, providing molecular mechanism for the mitochondrial quality surveillance system.