Elsevier

Mitochondrion

Volume 49, November 2019, Pages 259-268
Mitochondrion

Review
Linking mitochondrial dynamics, cristae remodeling and supercomplex formation: How mitochondrial structure can regulate bioenergetics

https://doi.org/10.1016/j.mito.2019.06.003Get rights and content

Highlights

  • Mitochondrial shape is a key factor in the determination of the bioenergetic capacity of cells.

  • Mitochondrial dynamics and cristae remodeling directly regulate mitochondrial respiratory function.

  • OPA1-mediated cristae remodeling promotes formation of ETC supercomplexes.

Abstract

The dynamic and fluid nature of mitochondria allows for modifications in mitochondrial shape, connectivity and cristae architecture. The precise balance of mitochondrial dynamics is among the most critical features in the control of mitochondrial function. In the past few years, mitochondrial shape has emerged as a key regulatory factor in the determination of the bioenergetic capacity of cells. This is mostly due to the recent discoveries linking changes in cristae organization with supercomplex assembly of the electron transport chain (ETC), also defined as the formation of respirosomes. Here we will review the most current advances demonstrating the impact of mitochondrial dynamics and cristae shape on oxidative metabolism, respiratory efficiency, and redox state. Furthermore, we will discuss the implications of mitochondrial dynamics and supercomplex assembly under physiological and pathological conditions.

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.

References (133)

  • C.D. Folmes

    Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming

    Cell Metab.

    (2011)
  • C.D. Folmes et al.

    Metabolic plasticity in stem cell homeostasis and differentiation

    Cell Stem Cell

    (2012)
  • S. Frank

    The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis

    Dev. Cell

    (2001)
  • M. Frenzel et al.

    Ageing alters the supramolecular architecture of OxPhos complexes in rat brain cortex

    Exp. Gerontol.

    (2010)
  • T.G. Frey et al.

    The internal structure of mitochondria

    Trends Biochem. Sci.

    (2000)
  • T.G. Frey et al.

    Insight into mitochondrial structure and function from electron tomography

    Biochim. Biophys. Acta

    (2002)
  • C. Frezza

    OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion

    Cell

    (2006)
  • R.W. Gilkerson et al.

    The cristal membrane of mitochondria is the principal site of oxidative phosphorylation

    FEBS Lett.

    (2003)
  • C. Glytsou

    Optic atrophy 1 is epistatic to the Core MICOS component MIC60 in mitochondrial cristae shape control

    Cell Rep.

    (2016)
  • L.A. Gómez et al.

    Supercomplexes of the mitochondrial electron transport chain decline in the aging rat heart

    Arch. Biochem. Biophys.

    (2009)
  • K. Itoh et al.

    Mitochondrial dynamics in neurodegeneration

    Trends Cell Biol.

    (2013)
  • Y.Y. Jang et al.

    A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche

    Blood

    (2007)
  • M. Jendrach

    Morpho-dynamic changes of mitochondria during ageing of human endothelial cells

    Mech. Ageing Dev.

    (2005)
  • M. Khacho

    Mitochondrial dynamics impacts stem cell identity and fate decisions by regulating a nuclear transcriptional program

    Cell Stem Cell

    (2016)
  • H. Lee et al.

    The short variant of the mitochondrial dynamin OPA1 maintains mitochondrial energetics and cristae structure

    J. Biol. Chem.

    (2017)
  • M. Liesa et al.

    Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure

    Cell Metab.

    (2013)
  • A. Lombardi

    Defining the transcriptomic and proteomic profiles of rat ageing skeletal muscle by the use of a cDNA array, 2D- and blue native-PAGE approach

    J. Proteome

    (2009)
  • K. von der Malsburg

    Dual role of mitofilin in mitochondrial membrane organization and protein biogenesis

    Dev. Cell

    (2011)
  • C.A. Mannella

    Structure and dynamics of the mitochondrial inner membrane cristae

    Biochim. Biophys. Acta

    (2006)
  • C.A. Mannella

    The relevance of mitochondrial membrane topology to mitochondrial function

    Biochim. Biophys. Acta

    (2006)
  • S. Meeusen

    Mitochondrial inner-membrane fusion and crista maintenance requires the dynamin-related GTPase Mgm1

    Cell

    (2006)
  • S. Montessuit

    Membrane remodeling induced by the dynamin-related protein Drp1 stimulates Bax oligomerization

    Cell

    (2010)
  • J. Nunnari et al.

    Mitochondria: in sickness and in health

    Cell

    (2012)
  • A. Olichon

    The human dynamin-related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter-membrane space

    FEBS Lett.

    (2002)
  • A. Olichon

    Loss of OPA1 perturbates the mitochondrial inner membrane structure and integrity, leading to cytochrome c release and apoptosis

    J. Biol. Chem.

    (2003)
  • C. Alexander

    OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28

    Nat. Genet.

    (2000)
  • A.K. Alkhaja

    MINOS1 is a conserved component of mitofilin complexes and required for mitochondrial function and cristae organization

    Mol. Biol. Cell

    (2012)
  • R. Anand

    The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission

    J. Cell Biol.

    (2014)
  • E. Balsa

    ER and nutrient stress promote assembly of respiratory chain supercomplexes through the PERK-eIF2α Axis

    Mol. Cell

    (2019)
  • G. Benard et al.

    Ultrastructure of the mitochondrion and its bearing on function and bioenergetics

    Antioxid. Redox Signal.

    (2008)
  • T.B. Blum et al.

    Dimers of mitochondrial ATP synthase induce membrane curvature and self-assemble into rows

    Proc. Natl. Acad. Sci. U. S. A.

    (2019)
  • T. Brandt

    Changes of mitochondrial ultrastructure and function during ageing in mice and Drosophila

    Elife

    (2017)
  • J.L. Burman

    Mitochondrial fission facilitates the selective mitophagy of protein aggregates

    J. Cell Biol.

    (2017)
  • V. Cavallucci

    Acute focal brain damage alters mitochondrial dynamics and autophagy in axotomized neurons

    Cell Death Dis.

    (2014)
  • D.C. Chan

    Fusion and fission: interlinked processes critical for mitochondrial health

    Annu. Rev. Genet.

    (2012)
  • A. Chauhan et al.

    The systems biology of mitochondrial fission and fusion and implications for disease and aging

    Biogerontology

    (2014)
  • H. Chen

    Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development

    J. Cell Biol.

    (2003)
  • H. Chen

    Titration of mitochondrial fusion rescues Mff-deficient cardiomyopathy

    J. Cell Biol.

    (2015)
  • Y. Chen et al.

    The tango of ROS and p53 in tissue stem cells

    Cell Death Differ.

    (2018)
  • S. Cipolat

    Martins de Brito, O., Dal Zilio, B. & Scorrano, L. OPA1 requires mitofusin 1 to promote mitochondrial fusion

    Proc. Natl. Acad. Sci. U. S. A.

    (2004)
  • Cited by (0)

    View full text