Regulation of Mitochondrial Function by the Actin Cytoskeleton.

María Illescas,Ana Peñas,Joaquín Arenas,Cristina Ugalde,Miguel A Martín

doi:10.3389/fcell.2021.795838

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.

Highlights

As a major component of the cellular structural network, relevant biological processes like cell division, migration, intracellular transport and organelle organization extensively rely on the dynamics and organization of the actin cytoskeleton
Mitochondria are present in eukaryotic cells and possess a characteristic architecture
Mitochondria are fundamental for reactive oxygen species (ROS) production, calcium homeostasis, heat production, cell proliferation or apoptosis (Brookes et al, 2004), and are the main site to important metabolic reactions including the citric acid cycle, amino acids interconversion or β-oxidation of fatty acids (Nunnari and Suomalainen, 2012), and ATP synthesis through the oxidative phosphorylation (OXPHOS) system (Reid et al, 1966)

Summary

Introduction

As a major component of the cellular structural network, relevant biological processes like cell division, migration, intracellular transport and organelle organization extensively rely on the dynamics and organization of the actin cytoskeleton. Actin filaments (F-actin) are formed by the polymerization of globular actin monomers (G-actin) in a neat disposition that allows filaments to be polarized Their remodeling is controlled by a repertoire of actin-binding proteins (ABPs), expressed in a tissue-dependent manner depending on where actin executes cell-specific functions (Lappalainen, 2016; Merino et al, 2020). These proteins regulate a wide spectrum of cellular processes, and are classified regarding their specific action mechanisms: maintenance of the G-actin monomers pool; G-actin nucleation and polymerization of actin filaments and branches; and filaments severing and depolymerization, mainly driven by cofilin and the gelsolin protein superfamily (Silacci et al, 2004). Mitochondria are fundamental for reactive oxygen species (ROS) production, calcium homeostasis, heat production, cell proliferation or apoptosis (Brookes et al, 2004), and are the main site to important metabolic reactions including the citric acid cycle, amino acids interconversion or β-oxidation of fatty acids (Nunnari and Suomalainen, 2012), and ATP synthesis through the oxidative phosphorylation (OXPHOS) system (Reid et al, 1966)

Objectives

Conclusion