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Review
. 2021 Dec 21:9:795838.
doi: 10.3389/fcell.2021.795838. eCollection 2021.

Regulation of Mitochondrial Function by the Actin Cytoskeleton

María Illescas  1 , Ana Peñas  1 , Joaquín Arenas  1   2 , Miguel A Martín  1   2 , Cristina Ugalde  1   2
Affiliations
Review

Regulation of Mitochondrial Function by the Actin Cytoskeleton

María Illescas et al. Front Cell Dev Biol. .

Abstract

The regulatory role of actin cytoskeleton on mitochondrial function is a growing research field, but the underlying molecular mechanisms remain poorly understood. Specific actin-binding proteins (ABPs), such as Gelsolin, have also been shown to participate in the pathophysiology of mitochondrial OXPHOS disorders through yet to be defined mechanisms. In this mini-review, we will summarize the experimental evidence supporting the fundamental roles of actin cytoskeleton and ABPs on mitochondrial trafficking, dynamics, biogenesis, metabolism and apoptosis, with a particular focus on Gelsolin involvement in mitochondrial disorders. The functional interplay between the actin cytoskeleton, ABPs and mitochondrial membranes for the regulation of cellular homeostasis thus emerges as a new exciting field for future research and therapeutic approaches.

Keywords: OXPHOS system; actin cytoskeleton; gelsolin; mitochondria; mitochondrial disease.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer EC declared a shared affiliation with the authors to the handling Editor.

Figures

FIGURE 1
FIGURE 1
Regulatory roles of actin cytoskeleton on mitochondrial function. (A) Schematic representation of a mitochondrion interacting with the endoplasmic reticulum (ER) at mitochondrial-endoplasmic reticulum contact sites (MERCS), where dynamin is recruited and fission events take place. (B) Under anti-apoptotic stimuli, actin-binding proteins interact with the voltage-dependent anion channel 1 (VDAC1) in the outer mitochondrial membrane (OMM), preventing actin filaments oligomerization and apoptosis; conversely, actin polymerization favors VDAC oligomerization and induces the apoptotic pathway. (C) Actin cytoskeleton is represented at MERCS, together with ABPs (INF2, Spire1C) and OMM proteins involved in mitochondrial dynamics (MFN1/2). Actin and myosin II localization at MERCSs initiates Drp1 recruitment, which binding to Drp1 receptors (Fis1, MUD49/50, MFF) leads to mitochondrial fission. (D) Actin interacts with mitochondrial respiratory chain (MRC) complexes III and IV in the matrix, controlling the association and dissociation of cytochrome c; and together with myosinII, actin regulates the distribution of mitochondrial nucleoids.
See this image and copyright information in PMC

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