Regulation of Mitochondrial Structure and Dynamics by the Cytoskeleton and Mechanical Factors

Abstract

Mitochondria supply cells with energy in the form of ATP, guide apoptosis, and contribute to calcium buffering and reactive oxygen species production. To support these diverse functions, mitochondria form an extensive network with smaller clusters that are able to move along microtubules aided by motor proteins. Mitochondria are also associated with the actin network, which is involved in cellular responses to various mechanical factors. In this review, we discuss mitochondrial structure and function in relation to the cytoskeleton and various mechanical factors influencing cell functions. We first summarize the morphological features of mitochondria with an emphasis on fission and fusion as well as how network properties govern function. We then review the relationship between the mitochondria and the cytoskeletal structures, including mechanical interactions. We also discuss how stretch and its dynamic pattern affect mitochondrial structure and function. Finally, we present preliminary data on how extracellular matrix stiffness influences mitochondrial morphology and ATP generation. We conclude by discussing the more general role that mitochondria may play in mechanobiology and how the mechanosensitivity of mitochondria may contribute to the development of several diseases and aging.

Mitochondrial Deformation During the Cardiac Mechanical Cycle

“…Intracellular organelles are arranged between strands of the contractile filament lattice, within a network of rigid and elastic nonsarcomeric cytoskeletal filaments. These organelles are influenced by deformations resulting from passive cardiomyocyte stretch and active shortening, a process aided by cytoskeletal filaments that bear and transmit mechanical loads throughout the cell (Bartolak‐Suki et al, ; Ingber, ; Robison et al, ). As shown for the surface sarcolemma (Kohl et al, ; Pfeiffer et al, ), some intracellular membranous structures, such as T‐tubules, contain “spare membrane” in the shape of caveolae (Burton et al, ).…”

Crosstalk between mitochondria, calcium channels and actin cytoskeleton modulates noradrenergic activity of locus coeruleus neurons

“…It is known that mitochondria are directly involved with inflammation as well as [Ca 2+ ] c deregulation (Bartolak‐Suki et al . ; Georgieva et al . ).…”

“…; Bartolak‐Suki et al . ). Thus, it seems likely that L‐type Ca 2+ channels are linked to mitochondrial function and could modulate the content of free radicals into a cell.…”

“…; Bartolak‐Suki et al . ) and Ca 2+ ‐dependent signalling pathways via their intracellular Ca 2+ buffering capacity (Gunter et al . , ; Ishii et al .…”

“…Key intracellular components underlying LC function include mitochondria. These subserve a crucial role in energy production (Lehninger et al 2008;Bartolak-Suki et al 2017) and Ca 2+ -dependent signalling pathways via their intracellular Ca 2+ buffering capacity (Gunter et al 2000(Gunter et al , 2004Ishii et al 2006). They have also been implicated in pathologies such as neuronal death (Randall and Thayer 1992), oxidative stress (Andreyev et al 2005) and certain neurodegenerative diseases (Vanitallie 2008).…”