Microtubules Are Essential for Mitochondrial Dynamics–Fission, Fusion, and Motility–in Dictyostelium discoideum

Abstract

Mitochondrial function is dependent upon mitochondrial structure which is in turn dependent upon mitochondrial dynamics, including fission, fusion, and motility. Here we examined the relationship between mitochondrial dynamics and the cytoskeleton in Dictyostelium discoideum. Using time-lapse analysis, we quantified mitochondrial fission, fusion, and motility in the presence of cytoskeleton disrupting pharmaceuticals and the absence of the potential mitochondria-cytoskeleton linker protein, CluA. Our results indicate that microtubules are essential for mitochondrial movement, as well as fission and fusion; actin plays a less significant role, perhaps selecting the mitochondria for transport. We also suggest that CluA is not a linker protein but plays an unidentified role in mitochondrial fission and fusion. The significance of our work is to gain further insight into the role the cytoskeleton plays in mitochondrial dynamics and function. By better understanding these processes we can better appreciate the underlying mitochondrial contributions to many neurological disorders characterized by altered mitochondrial dynamics, structure, and/or function.

The Dictyostelium model for mitochondrial biology and disease

“…Mitochondria undergo continuous cycles of fusion and fission and are redistributed within the cell to areas requiring energy production (Eisner et al, 2018). Mitochondrial movement, fusion and fission are dependent on the cell cytoskeleton, both actin and microtubular, and mediated by actin and microtubule motor proteins (Woods et al, 2016).…”

“…Despite a similar result of interconnected mitochondria as in the case of dymA-mutants, this seemed not to be due to cytoskeletal disruption, but to the late blocking of mitochondrial outer membrane fission (Fields et al, 2002). Previously hypothesised to function as a mitochondria-cytoskeleton linker protein, CluA has since been demonstrated not to be required for mitochondrial motility but does play an as yet unidentified role in mitochondrial fusion and fission (Woods et al, 2016). While it is known that FszA, FszB, and CluA are all essential for mitochondrial fusion and fission, it is not known whether these can account for all of the mitochondrial division activity, since there are no triple mutants available.…”

“…Pharmacological disruption of microtubules demonstrated that they are the primary cytoskeletal element involved in D. discoideum mitochondrial movement and distribution (Woods et al, 2016). Actin filaments appear to play a secondary role, affecting the number of mitochondria moving at one time, but not their movement speed or cellular distribution (Woods et al, 2016). The Ras-related GTPase Miro was shown in humans to play a role in the calcium-dependent regulation of mitochondrial transport along microtubules.…”

The past, present and future of Dictyostelium as a model system

“…Arginylation, a post-translational modification regulated by the conserved enzyme arginyl-tRNA-protein (Ate1), has been shown to control actin polymerization, affecting focal adhesion and motility (Batsios et al, 2019). Evidence has also been provided that microtubules control mitochondria fission, fusion and motility (Woods et al, 2016).…”

The slow force response to stretch: Controversy and contradictions

“…Microtubular integrity is required for stretch-induced mitochondrial hyperpolarization 22,23 and enhanced NOX2 1 activity. 24 Given the evidence regarding ROS as a signalling molecule in the SFR, the microtubular system, which has recently been shown to be involved in mitochondrial motility and function, 25,26 may be important.…”