Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Mar 15;304(6):R393-406.
doi: 10.1152/ajpregu.00584.2012. Epub 2013 Jan 30.

Mitochondrial morphology transitions and functions: implications for retrograde signaling?

Martin Picard  1 , Orian S Shirihai, Benoit J Gentil, Yan Burelle
Affiliations
Review

Mitochondrial morphology transitions and functions: implications for retrograde signaling?

Martin Picard et al. Am J Physiol Regul Integr Comp Physiol. .

Abstract

In response to cellular and environmental stresses, mitochondria undergo morphology transitions regulated by dynamic processes of membrane fusion and fission. These events of mitochondrial dynamics are central regulators of cellular activity, but the mechanisms linking mitochondrial shape to cell function remain unclear. One possibility evaluated in this review is that mitochondrial morphological transitions (from elongated to fragmented, and vice-versa) directly modify canonical aspects of the organelle's function, including susceptibility to mitochondrial permeability transition, respiratory properties of the electron transport chain, and reactive oxygen species production. Because outputs derived from mitochondrial metabolism are linked to defined cellular signaling pathways, fusion/fission morphology transitions could regulate mitochondrial function and retrograde signaling. This is hypothesized to provide a dynamic interface between the cell, its genome, and the fluctuating metabolic environment.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Hypothesized relationship linking mitochondrial morphology and function. Dynamic regulation of mitochondrial morphology involves regulated processes of fusion and fission, which modify mitochondrial function. Pro-fusion [mitofusin 1 and 2 (Mfn1, Mfn2), optic atrophy 1 (OPA1)] and pro-fission [dynamin-related protein (DRP1), fission 1 (Fis1)] core proteins modulate mitochondrial morphology and physiology. Altering the balance of fusion/fission dynamics results in mitochondrial elongation and branching (pro-fusion) or mitochondrial fragmentation (pro-fission). For detailed review of these processes, see Ref. . Listed on both sides of the figure are the putative functional consequences generally associated with mitochondrial fusion and fission. Insets: fluorescence microscopy images of mitochondria from cultured human myoblasts labeled with Mitotracker Green (45 min, 125 nM) depicting different states of mitochondrial morphology.
Fig. 2.
Fig. 2.
Potential consequences of altering the mitochondrial fusion and fission proteins in experimental systems. Mitochondrial fusion and fission proteins directly influence mitochondrial morphology and the architecture of the mitochondrial network but also influence other cellular processes that impact bioenergetics. These include the mitochondrial autophagic quality control processes (mitophagy), interactions with other intracellular structures (endo-/sarcoplasmic reticulum, cytoskeleton, lipid droplets), membrane interactions between mitochondria, transcriptional effects (transcriptional regulation of OXPHOS genes by Mfn2), and possibly other processes not depicted here. Experimental manipulation of mitochondrial dynamics proteins, especially if of long duration, may impact mitochondrial bioenergetics and downstream retrograde signals through mechanisms independent from mitochondrial morphology transitions. LD, lipid droplet; ER, endoplasmic reticulum.
Fig. 3.
Fig. 3.
Substrates of mitochondrial retrograde signaling. Shown are selected second messengers derived from mitochondrial function, which directly yield cellular effects (see first 5 headings under Mitochondrial Retrograde Signaling for discussion). Second messengers can in turn influence molecular targets that induce specific cellular effects. mPTP, mitochondrial permeability transition pore.
Fig. 4.
Fig. 4.
Potential role of mitochondrial morphology transitions as an integrating mechanism influencing intracellular signaling. Specific environmental stimuli and stresses impact cellular function via signaling mechanisms that may involve mitochondrial morphology transitions. Mitochondrial dynamics (fusion and fission) are linked to certain aspects of mitochondrial function. Mitochondrial dynamics could participate in both normal physiological adaptation (see circled 1) [e.g., promoting cell survival in response to nutrient deprivation (54, 112)], and to pathological responses (see circled 2) [e.g., hyperglycemia-induced cell death death (163), diabetic insulin resistance in skeletal muscle (76)]. Metabolic states of “undersupply” (negative energy balance) and “oversupply” (positive energy balance) tend to induce fusion and fragmentation of the mitochondrial network, respectively, possibly accounting for the health effects of physical activity/inactivity and energy intake (116).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Acin-Perez R, Gatti DL, Bai Y, Manfredi G. Protein phosphorylation and prevention of cytochrome oxidase inhibition by ATP: coupled mechanisms of energy metabolism regulation. Cell Metab 13: 712–719, 2011 - PMC - PubMed
    1. Amati-Bonneau P, Valentino ML, Reynier P, Gallardo ME, Bornstein B, Boissiere A, Campos Y, Rivera H, de la Aleja JG, Carroccia R, Iommarini L, Labauge P, Figarella-Branger D, Marcorelles P, Furby A, Beauvais K, Letournel F, Liguori R, La Morgia C, Montagna P, Liguori M, Zanna C, Rugolo M, Cossarizza A, Wissinger B, Verny C, Schwarzenbacher R, Martin MA, Arenas J, Ayuso C, Garesse R, Lenaers G, Bonneau D, Carelli V. OPA1 mutations induce mitochondrial DNA instability and optic atrophy ‘plus’ phenotypes. Brain 131: 338–351, 2008 - PubMed
    1. Anderson EJ, Lustig ME, Boyle KE, Woodlief TL, Kane DA, Lin CT, Price JW, 3rd, Kang L, Rabinovitch PS, Szeto HH, Houmard JA, Cortright RN, Wasserman DH, Neufer PD. Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J Clin Invest 119: 573–581, 2009 - PMC - PubMed
    1. Arnoult D. Mitochondrial fragmentation in apoptosis. Trends Cell Biol 17: 6–12, 2007 - PubMed
    1. Aure K, Fayet G, Leroy JP, Lacene E, Romero NB, Lombes A. Apoptosis in mitochondrial myopathies is linked to mitochondrial proliferation. Brain 129: 1249–1259, 2006 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources

-