Elsevier

Mitochondrion

Volume 49, November 2019, Pages 284-288
Mitochondrion

Review
Mitochondrial interaction with the endosomal compartment in endocytosis and mitochondrial transfer

https://doi.org/10.1016/j.mito.2019.05.003Get rights and content

Highlights

  • Mitochondria physically and functionally interact with the endoplasmic reticulum (ER) and endosomes.

  • These interactions are emerging as part of a larger array of intracellular transport mechanisms.

  • Mitochondria-endosomes interactions regulate metabolism, quality control mechanisms and innate immunity.

  • Mitochondrial proteins are exported in extracellular vesicle as quality control mechanism and/or for cell-cell communication.

Abstract

Mitochondria are essential organelles required for cellular processes ranging from energy production to cellular differentiation. To perform these functions, mitochondria physically and functionally interact with other organelles such as the endoplasmic reticulum (ER) and endosomes. While the role of ER-mitochondria contact sites is well established, the interaction between mitochondria and endosomes has only recently been reported. These interactions are involved in lipid and ion transfer and potentially play a crucial role in mitochondria quality control and the release of mitochondrial components within extracellular vesicles. Here, we will discuss the current view of mitochondria-endosome interaction, both physically and functionally.

Introduction

Mitochondria play a key role in metabolic regulation including, but not limited to, ATP generation. Moreover, work over the last decades has demonstrated a variety of crucial roles for this organelle, from Ca2+ homeostasis to apoptosis and stem cell maintenance (Friedman and Nunnari, 2014; Zhang et al., 2018). It has also become clear that mitochondria physically and functionally interact with several other organelles (Daniele and Schiaffino, 2014; Todkar et al., 2017). These interactions establish the connection between organelles essential for homeostatic control of cellular processes. For example, ER-mitochondria contact sites regulate mitochondrial division, Ca2+ homeostasis, as well as lipid transfer between the two organelles (Daniele and Schiaffino, 2014; Elbaz and Schuldiner, 2011). More recently, mitochondria have been shown to interact with the endosomal compartment, from early endosomes containing endocytosed material (Charman et al., 2010; Das et al., 2016; Hamdi et al., 2016; Sheftel et al., 2007), to lysosomes that break down this material for subsequent usage by the cell (Aston et al., 2017; Elbaz-Alon et al., 2014; Han et al., 2017; Hönscher et al., 2014; Wong et al., 2018). Two main roles are emerging for these interactions. First, consistent with the degradative function of lysosomes, mitochondria-endosomes interactions are involved in stress-responses and mitochondria quality control (McBride, 2018). Second, these interactions are emerging as part of a larger array of transport mechanisms that shuttle ions and metabolites across cytoplasmic organelles (Soto-Heredero et al., 2017; Todkar et al., 2017). In addition, mitochondrial activity is required for proper functioning of lysosomes (Baixauli et al., 2015; Demers-Lamarche et al., 2016). In this review, we will discuss the roles and potential mechanisms underlying the interaction between mitochondria and the endosomal compartment, as well as their relationship with mitochondrial transfer as a cell-to cell communication device.

Section snippets

Mitochondria and endosomes

Mitochondria produce ATP and important metabolic intermediates such as Acetyl-CoA, from soluble molecules such as glucose and amino acids that are taken up by cells and distributed to organelles through members of the Solute Carriers (SLC) family of transporters (Lin et al., 2015). Mitochondria also perform key steps in the synthesis of steroid hormones (Miller, 2013) and Iron-Sulfur clusters, inorganic cofactors required for a large array of biochemical reactions (Braymer and Lill, 2017).

Endocytosis and mitochondrial dynamics

In healthy cells, mitochondria exist as a highly interconnected network that is regulated through mitochondrial dynamics (Friedman and Nunnari, 2014). Mitochondrial dynamics, which includes mitochondrial fission and fusion, is required for the proper maintenance and segregation of mtDNA, and regulates key cellular processes such as cellular differentiation and apoptosis (Friedman and Nunnari, 2014). In addition, mitochondrial degradation through mitophagy requires mitochondrial fission, where

Mitochondria quality control, transfer and immunity

Given the above, it is not surprising that accumulation of dysfunctional mitochondria leads to impaired metabolism, increased ROS production and altered cellular functions. In addition, defective mitochondrial components can directly activate an inflammatory response under some circumstances, likely as a consequence of their bacterial origin. For example, mitochondrial damage leads to the release of mtDNA to the cytosol, where it acts as a Damage-Associated Molecular Pattern (DAMP) that

Conclusion

While mitochondria are classically seen as the powerhouse of the cell, work over the last decades has revealed that they in fact perform a large number of functions. Many of the recently identified roles of mitochondria require intimate communication with other organelles, including the endosomal compartment. Mitochondrial and lysosomal dysfunction are individually associated with a wide range of diseases but our understanding of how the interaction between the two organelles participates in

Acknowledgements

We thank Hema Saranya Ilamathi, Priya Gatti and Pritha Mukherjee for insightful comments on the manuscript. This work was supported by grants from the Natural Sciences and Engineering Research Council of Canada and the Fondation UQTR. KT is a recipient of a Queen Elizabeth II Diamond Jubilee scholarship and a Fonds du Québec-Santé scholarship. LC is a recipient of a Fonds du Québec-Santé scholarships.

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