Two distinct actin filament populations have effects on mitochondria, with differences in stimuli and assembly factors

Abstract

statement: Mitochondrial depolarization induces Arp2/3 complex-dependent actin clouds that restrain mitochondrial shape changes induced by Oma1 on the inner mitochondrial membrane. A distinct actin network stimulates mitochondrial fission in response to calcium. Fung et al Actin and Mitochondria 2 AbstractRecent studies show that mitochondria and actin filaments work together in two contexts: 1) increased cytoplasmic calcium induces cytoplasmic actin polymerization that stimulates mitochondrial fission, and 2) mitochondrial depolarization causes actin assembly around mitochondria, with roles in mitophagy. It is unclear whether these two processes utilize similar actin assembly mechanisms. Here, we show that these are distinct actin assembly mechanisms in the acute phase after treatment (<10 min). Calcium-induced actin assembly is INF2-dependent and Arp2/3 complex-independent, whereas depolarization-induced actin assembly is Arp2/3 complexdependent and INF2-independent. The two types of actin polymerization are morphologically distinct, with calcium-induced filaments throughout the cytosol and depolarization-induced filaments as "clouds" around depolarized mitochondria. We have previously shown that calciuminduced actin stimulates increases in both mitochondrial calcium and recruitment of the dynamin GTPase Drp1. In contrast, depolarization-induced actin is temporally-associated with extensive mitochondrial dynamics that do not result in mitochondrial fission, but in circularization of the inner mitochondrial membrane (IMM). These dynamics are dependent upon the protease Oma1 and independent of Drp1. Actin cloud inhibition causes increased IMM circularization, suggesting that actin clouds limit these dynamics. Fung et alActin and Mitochondria

Nanoscale details of mitochondrial fission revealed by cryo-electron tomography

“…Interestingly, we rarely found any free actin filament ends in constriction zones, or even beyond in the larger volume of the tomograms, suggesting that these long filaments are nucleated elsewhere in the cell. Previously, Arp2/3, a major nucleator of actin branching, was shown to be involved in mitochondrial fission triggered by CCCP, a drug similar to FCCP (Fung et al, 2019). The actin filaments we observed, however, were linear with no observable branching, suggesting that Arp2/3 is not organizing F-actin networks locally at division sites.…”

Parallel kinase pathways stimulate actin polymerization at depolarized mitochondria

“…One recently identified population of actin filaments polymerizes around damaged mitochondria, 3,4 which we refer to as acute damage-induced actin (ADA). ADA is transient, being triggered within 2 min of stimulation and fully depolymerized in 10 min.…”

Local complement factor H protects kidney endothelial cell structure and function

“…Actin and mitochondria interact during actin polymerization, participating in mitochondrial communication and dynamics. 51 Our results show that actin remodeling occurred in EnCs in the absence of FH. Actin changes occurred when the wild-type KEnCs are treated with C5a, similar to that observed in brain EnCs.…”