ReviewLinking mitochondrial dynamics, cristae remodeling and supercomplex formation: How mitochondrial structure can regulate bioenergetics
Section snippets
The dynamic nature of the mitochondrion and the enigma of structure-function relations
The modern-day view of mitochondria defines this organelle as a multifaceted center with an array of functions, from cell signaling and calcium homeostasis to regulation of cell death and reactive oxygen species (ROS) (Kamer and Mootha, 2015; Tait and Green, 2012; Yu and Pekkurnaz, 2018). Despite this diversity in functions, mitochondria remain best acknowledged as the chief energy providers for the cell. For this reason, studies from the past decade have been focused on understanding the
Mitochondrial fission
The dynamic nature of mitochondria is controlled by a series of dynamin-like GTPase proteins that mediate fission and fusion events. The fission process involves the division of mitochondria at the inner and outer membrane through the action of the large GTPase, dynamin related protein 1 (DRP1), as well as other factors including Fis1, MFF, MiD49 and MiD51 (Smirnova et al., 2001a; Losón et al., 2013; Otera et al., 2016; Smirnova et al., 2001b). In addition to these proteins, recent studies
Defining mitochondrial ultrastructure
Apart from general changes in mitochondrial length and connectivity, the IMM has a high degree of complexity and can undergo structural modifications. The inner membrane of mitochondria is composed of two main sections, the inner boundary membrane (IBM) and the cristae (Frey and Mannella, 2000) (Fig. 2, Fig. 3). Here, cristae are defined as lamellar invaginations with curved edges formed from the IMM and are connected to the inner boundary membrane by the cristae junctions. The cristae
The interplay of mitochondrial dynamics, cristae remodeling and supercomplex assembly
Since the discovery of mitochondrial dynamics, there has been a consistent association between fission and fusion events and cell survival versus cell death. In fact, an enhancement in cell survival and mitochondrial function has been historically associated with mitochondrial fusion, particularly in response to conditions of cell stress, not only as an indication of ameliorated mitochondrial health or fitness but also as a means of regulating metabolism (Benard and Rossignol, 2008; Chan, 2012;
Mitochondrial dynamics, cristae structure, and supercomplexes in aging
During the aging process, mitochondrial dysfunction is observed and the regulatory balance of mitochondrial dynamics is often disrupted, leading to increased mitochondrial fragmentation in aging cells (Jendrach et al., 2005; Chauhan et al., 2014; Scheckhuber et al., 2007). In fact, dysregulation of mitochondrial dynamics is thought to play a role in age-related disorders and higher susceptibility of cells to various stress conditions during progressive aging (Tezze et al., n.d.). As such, loss
A perspective on mitochondrial dynamics and bioenergetic regulation in stem cells
Throughout this review the role of mitochondrial dynamics, cristae remodeling and supercomplex formation in post-mitotic cell homeostasis have been discussed. These mitochondrial processes are also essential for stem cell vitality and are additionally required for stem cell function and differentiation. In general, stem cells must undergo necessary metabolic changes in order to commit and differentiate to specific cell fates. This process, referred to as “metabolic reprogramming”, involves the
Concluding remarks
An imbalance in mitochondrial dynamics, which is often observed in many degenerative disorders, during aging and different stress conditions, is an important element that contributes to cell death and energy crisis. Though the impact of mitochondrial dynamics on cell death signaling have been thoroughly investigated, studies now reveal that mitochondrial structure can directly regulate cellular metabolism. Alteration in mitochondrial dynamics and cristae structure can be now viewed as a
Acknowledgments
This work was supported by an NSERC Discovery grant to MK. We thank Madhevee Thumiah-Mootoo and Tina Podnic for insightful comments.
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