Integrating mitochondrial organization and dynamics with cellular architecture
Introduction
Mitochondria form tubular networks that exhibit a wide range of geometries depending on cell type and environmental conditions. The organization of mitochondrial networks is generated through constant dynamics of tubule fission and fusion, movements along cytoskeletal tracks, and mechanisms that position mitochondria in specific regions of the cell (reviews listed below). Together these mechanisms ensure that mitochondria are distributed throughout the cell, are segregated properly upon cell division, and are at the right place at the right time to provide their essential metabolic and signaling functions. Mitochondria directly interact with other organelles and subcellular structures, such as the endoplasmic reticulum (ER) and the cytoskeleton and these interactions allow mitochondria to both be influenced by, and in turn, contribute to generating cellular architecture. There have been numerous recent reviews documenting how mitochondria are shaped, positioned, and interact with the ER, to which we refer readers for more information [1, 2, 3, 4, 5, 6]. In this review we will begin with a focus on the most recent studies of how mitochondrial organization influences mitochondrial DNA (mtDNA) distribution (Figure 1), not covered in these reviews. We will then expand on how mitochondrial organization and dynamics are integrated with internal cellular architecture (Figure 2) by highlighting specific examples in the recent literature.
Section snippets
Organization and distribution of mtDNA
Mitochondria carry their own genome, which encodes proteins required for oxidative phosphorylation (OXPHOS) along with its own rRNAs and tRNAs that are required for translation of these transcripts. The mtDNA is organized into nucleoprotein structures called nucleoids, which are distributed throughout the mitochondrial network. The number of mtDNA copies can vary anywhere from 1 to 10 copies per nucleoid and the number of nucleoids ranges from 10 to 1000 per cell, depending on cell type and
Emerging roles of actin in mitochondrial organization and dynamics
It is well established that in some organisms, including budding yeast and plants, mitochondria primarily move along the actin cytoskeleton and thus the role of actin and actin related mechanisms such as myosin motility and actin polymerization are known to be crucial for mitochondrial motility and positioning [4, 20]. In mammalian cells mitochondria move primarily along microtubules via microtubule motors (Figure 2a). However, there is continuing evidence that mitochondrial organization in
Mitochondria interacting with other intracellular structures
The direct interactions between mitochondria and ER have long been observed and extensively studied [2, 3]. Less widely known are the interactions between mitochondria and other organelles and intracellular structures (Figure 2b). For example, lipid droplets have been observed to be closely associated with mitochondria in numerous cell types (reviewed in [29]). However, interactions between mitochondria and other organelles go beyond being in close physical contact. Small cargo selective
Mitochondrial organization impacting cellular architecture
Mitochondria not only interact with and exchange materials with other cellular organelles, but their organization itself can also have a direct impact on cellular architecture and function. The most classic examples involve mitochondrial positioning in contracting muscle cells and in neurons. In muscle cells, most of the mitochondria are tightly aligned with the myofibrils to provide high ATP concentrations very close to the site that needs them most during contraction [37]. In neurons,
Conclusions
A lot of recent research on mitochondrial organization and dynamics shares the theme that mitochondria are not isolated entities in the cell and instead are intimately intertwined with other organelles. Mitochondrial organization and dynamics are not only greatly impacted by cellular architecture but also contribute to it. Given that mitochondria are so central not just to ATP production but also other essential metabolic processes, it makes a lot of sense that they are very integrated into all
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
We thank Irina Mueller and Matheus Viana for helpful comments and discussion.
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