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.

Highlights

  • Mitochondria are highly specialized eukaryotic organelles responsible for producing the majority of a cell’s adenosine triphosphate (ATP)

  • To determine if there was a synergistic effect between actin and microtubules, mitochondrial morphology of both strains was analyzed when the cells were exposed to nocodazole and latrunculin-B simultaneously

  • Our results show that dimethyl sulfoxide (DMSO) treated cluA− mitochondria fission and fusion rates were balanced (p = 1.0) and similar to the ethanol control rates, which were balanced (p = 1.0; Table 2). cluA− strains treated with nocodazole showed significantly lower fission and fusion compared to the DMSO control, 81 and 78% respectively

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Summary

Introduction

Mitochondria are highly specialized eukaryotic organelles responsible for producing the majority of a cell’s adenosine triphosphate (ATP) They play a vital role in many other cellular processes, such as the synthesis of heme groups and the regulation of membrane potential, calcium homeostasis, apoptosis, and cell differentiation (Mitchell, 1961; Frezza et al, 2006; Lill and Mühlenhoff, 2008; Baughman et al, 2011; De Stefani et al, 2011; Martinou and Youle, 2011; Maeda and Chida, 2013). The appropriate morphologies are maintained by fission and fusion events (Nunnari et al, 1997; Bleazard et al, 1999; Gilson et al, 2003; Karbowski and Youle, 2003; Twig and Shirihai, 2011; El Zawily et al, 2014).

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