Myosin VI-Dependent Actin Cages Encapsulate Parkin-Positive Damaged Mitochondria.

TitleMyosin VI-Dependent Actin Cages Encapsulate Parkin-Positive Damaged Mitochondria.
Publication TypeJournal Article
Year of Publication2018
AuthorsKruppa, AJ, Kishi-Itakura, C, Masters, TA, Rorbach, JE, Grice, GL, Kendrick-Jones, J, Nathan, JA, Minczuk, MA, Buss, F
JournalDev Cell
Volume44
Issue4
Pagination484-499.e6
Date Published2018 Feb 26
ISSN1878-1551
Abstract

Mitochondrial quality control is essential to maintain cellular homeostasis and is achieved by removing damaged, ubiquitinated mitochondria via Parkin-mediated mitophagy. Here, we demonstrate that MYO6 (myosin VI), a unique myosin that moves toward the minus end of actin filaments, forms a complex with Parkin and is selectively recruited to damaged mitochondria via its ubiquitin-binding domain. This myosin motor initiates the assembly of F-actin cages to encapsulate damaged mitochondria by forming a physical barrier that prevents refusion with neighboring populations. Loss of MYO6 results in an accumulation of mitophagosomes and an increase in mitochondrial mass. In addition, we observe downstream mitochondrial dysfunction manifesting as reduced respiratory capacity and decreased ability to rely on oxidative phosphorylation for energy production. Our work uncovers a crucial step in mitochondrial quality control: the formation of MYO6-dependent actin cages that ensure isolation of damaged mitochondria from the network.

DOI10.1016/j.devcel.2018.01.007
Alternate JournalDev. Cell
Citation Key10.1016/j.devcel.2018.01.007
PubMed ID29398621