How cytoskeletal proteins regulate mitochondrial energetics in cell physiology and diseases

Abstract

Mitochondria are ubiquitous organelles that play a pivotal role in the supply of energy through the production of adenosine triphosphate in all eukaryotic cells. The importance of mitochondria in cells is demonstrated in the poor survival outcomes observed in patients with defects in mitochondrial gene or RNA expression. Studies have identified that mitochondria are influenced by the cell's cytoskeletal environment. This is evident in pathological conditions such as cardiomyopathy where the cytoskeleton is in disarray and leads to alterations in mitochondrial oxygen consumption and electron transport. In cancer, reorganization of the actin cytoskeleton is critical for trans-differentiation of epithelial-like cells into motile mesenchymal-like cells that promotes cancer progression. The cytoskeleton is critical to the shape and elongation of neurons, facilitating communication during development and nerve signalling. Although it is recognized that cytoskeletal proteins physically tether mitochondria, it is not well understood how cytoskeletal proteins alter mitochondrial function. Since end-stage disease frequently involves poor energy production, understanding the role of the cytoskeleton in the progression of chronic pathology may enable the development of therapeutics to improve energy production and consumption and slow disease progression. This article is part of the theme issue ‘The cardiomyocyte: new revelations on the interplay between architecture and function in growth, health, and disease’.