Simple to Complex: The Role of Actin and Microtubules in Mitochondrial Dynamics in Amoeba, Yeast, and Mammalian Cells

Abstract

Mitochondria are complex organelles that provide energy for the cell in the form of adenosine triphosphate (ATP) and have very specific structures. For most organisms, this is a reticular or tubular mitochondrial network, while others have singular oval-shaped organelles. Nonetheless, maintenance of this structure is dependent on the mitochondrial dynamics, fission, fusion, and motility. Recently, studies have shown that the cytoskeleton has a significant role in the regulation of mitochondrial dynamics. In this review, we focus on microtubules and actin filaments and look at what is currently known about the cytoskeleton’s role in mitochondrial dynamics in complex models like mammals and yeast, as well as what is known in the simple model system, Dictyostelium discoideum. Understanding how the cytoskeleton is involved in mitochondrial dynamics increases our understanding of mitochondrial disease, especially neurodegenerative diseases. Increases in fission, loss of fusion, and fragmented mitochondria are seen in several neurodegenerative diseases such as Parkinson’s, Alzheimer’s, and Huntington’s disease. There is no known cure for these diseases, but new therapeutic strategies using drugs to alter mitochondrial fusion and fission activity are being considered. The future of these therapeutic studies is dependent on an in-depth understanding of the mechanisms of mitochondrial dynamics. Understanding the cytoskeleton’s role in dynamics in multiple model organisms will further our understanding of these mechanisms and could potentially uncover new therapeutic targets for these neurodegenerative diseases.

Mitochondria: At the crossroads between mechanobiology and cell metabolism

“…A number of molecular complexes involved in mammalian mitochondrial cristae remodeling, fission and fusion have been identified. The detailed mechanisms of mitochondrial fission and fusion have been extensively reviewed previously (Chan, 2006; Pernas & Scorrano, 2016; Wai & Langer, 2016; Jones & Naylor, 2022). High molecular weight guanosine triphosphatases (GTPases) are key regulators of mitochondrial morphodynamics.…”

Mitochondrial Dynamics in Neurodegenerative Diseases: Unraveling the Role of Fusion and Fission Processes

“…Contemporary research also explores potential therapeutics capable of modulating these mitochondrial transformations. Compounds that influence either mitochondrial fusion or fission are promising contenders for novel therapeutic strategies targeting NDs [15,74,148]. For instance, mitochondrial division inhibitors like Mdivi-1 have demonstrated neuroprotective capabilities in conditions induced by excitotoxicity [142,143,149,150].…”

“…An interruption in this delicate balance, akin to a dissonant note in a musical composition, has the potential to trigger cellular disharmony and disease. Evident in various neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases [74], the elevation of fission, reduction in fusion, and the presence of fragmented mitochondria imply that mitochondrial fragmentation can indeed function as a disease-state biomarker [75].…”

A Perspective: Challenges in Dementia Research

“…Thus, it is necessary to have multiple overlapping models beginning at the smallest scale. There has been much work on the dynamics of protein folding and molecular dynamics [ 130 , 131 , 132 ] that has been stretched to the organelle level [ 133 ]. Beginning with this, models of the relevant aspects of single cell behavior [ 134 , 135 ] can be created and matched to cellular models.…”