Mitochondria: Starving to reach quorum?

Picard, Martin; Burelle, Yan

doi:10.1002/bies.201100179

Cited by 18 publications

(12 citation statements)

References 31 publications

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“…Together, these reports demonstrate that inhibiting the mitochondrial fission machinery prevents mitochondrial fragmentation and blocks specific retrograde signals (e.g., ROS) and downstream cellular processes ranging from 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).…”

Section: Nadmentioning

confidence: 96%

“…4). The notion that mitochondrial morphology transitions directly control cellular signals is reinforced by the fact that mitochondrial fission and fusion constitute early events having downstream consequences on cell function and survival (112). For example, inhibiting mitochondrial fragmentation in vitro and in vivo with the DRP1 inhibitor Mdivi-1 conferred protection against the deleterious effects of hyperglycemia/hyperlipidemia on skeletal muscle (insulin resistance) (76), suggesting that mitochondrial fragmentationinduced ROS production plays a causal role in the development of insulin resistance with metabolic oversupply in vivo (i.e., hyperglycemia) (3,76).…”

Section: Nadmentioning

confidence: 99%

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Mitochondrial morphology transitions and functions: implications for retrograde signaling?

Picard

Shirihai

Gentil

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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264

193

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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. mitochondrial dynamics; morphology; fusion and fission; bioenergetics; retrograde signaling MITOCHONDRIA are crucial organelles involved in cellular energy production and in the regulation of numerous aspects of cellular activity, including, but not limited to, apoptosis, Ca 2ϩ signaling, and redox homeostasis (41). Over the last decade, mitochondria have moved to the forefront of cell biology research for their ability to undergo regulated events of membrane fusion and fission, which remodel the architecture of the mitochondrial network within the cytoplasm (43,36,146). Processes of mitochondrial fusion and fission are collectively termed mitochondrial dynamics. Importantly, abnormal mitochondrial dynamics cause bioenergetic defects (26), induce embryonic lethality in transgenic animal models (27), and underly a heterogenous group of human diseases (164), attesting to the pivotal role of these processes in physiopathology (25,50,91). In addition, experimental work has shown that mitochondrial dynamics are involved in regulating cellular activity and that mitochondria participate in important cellular signaling pathways (136,158).Mitochondrial retrograde signaling is defined as the transfer of information from mitochondria to the cytoplasm and nucleus. Retrograde signaling pathways have been established to occur in response to metabolic perturbations, with the aim to trigger adaptive cellular responses orchestrated by coordinated changes in gene expression (reviewed in Refs. 21 and 93). Among the retrograde signals produced by mitochondria that are known to regulate different aspects of cellular activity, the most studied include reactive oxygen species (ROS), pro-apoptotic molecules, ATP/ADP/AMP, metabolic intermediates (NAD ϩ /NADH), and Ca 2ϩ (20,39,58). From recent discoveries revealing that mitochondrial dynamics regulate cellular activity in response to various stressors, it is hypothesized that changes in mitochondrial morphology regulate, either directly or indirectly, various aspects of mitochondrial funct...

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Section: Nadmentioning

confidence: 96%

Section: Nadmentioning

confidence: 99%

Mitochondrial morphology transitions and functions: implications for retrograde signaling?

Picard

Shirihai

Gentil

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

264

193

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“…In this article we consider several hypotheses for an increase in [ATP] in highly fused mitochondrial states; in this table we only discuss hypothesis (iv): the others are discussed in sections S2. 2 mitochondria to synchronize gene expression [1,88] or improve the health of the mitochondrial population by allowing mitochondria to complement each other's deficiencies [89,90] (functional complementation).…”

Section: Increased Buffering Against Perturbationsmentioning

confidence: 99%

What is the function of mitochondrial networks? A theoretical assessment of hypotheses and proposal for future research

2015

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Mitochondria can change their shape from discrete isolated organelles to a large continuous reticulum. The cellular advantages underlying these fused networks are still incompletely understood. In this paper, we describe and compare hypotheses regarding the function of mitochondrial networks. We use mathematical and physical tools both to investigate existing hypotheses and to generate new ones, and we suggest experimental and modelling strategies. Among the novel insights we underline from this work are the possibilities that (i) selective mitophagy is not required for quality control because selective fusion is sufficient; (ii) increased connectivity may have non-linear effects on the diffusion rate of proteins; and (iii) fused networks can act to dampen biochemical fluctuations. We hope to convey to the reader that quantitative approaches can drive advances in the understanding of the physiological advantage of these morphological changes.

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“…Not unlike their “social” bacterial ancestors mitochondria undergo a form of quorum sensing (Picard and Burelle, 2012). Specialized inter-mitochondrial junctions also exist between adjacent mitochondria where cristae ultratructure becomes coordinated between neighboring organelles, indicating the exchange of information (Picard et al, 2015b).…”

Section: Introductionmentioning

confidence: 99%

The rise of mitochondria in medicine

2016

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Once considered exclusively the cell's powerhouse, mitochondria are now recognized to perform multiple essential cellular functions beyond energy production, impacting most areas of cell biology and medicine. Since the emergence of molecular biology and the discovery of pathogenic mitochondrial DNA defects in the 1980's, research advances have revealed a number of common human diseases which share an underlying pathogenesis involving mitochondrial dysfunction. Mitochondria undergo function-defining dynamic shape changes, communicate with each other, regulate gene expression within the nucleus, modulate synaptic transmission within the brain, release molecules that contribute to oncogenic transformation and trigger inflammatory responses systemically, and influence the regulation of complex physiological systems. Novel “mitopathogenic” mechanisms are thus being uncovered across a number of medical disciplines including genetics, oncology, neurology, immunology, and critical care medicine. Increasing knowledge of the bioenergetic aspects of human disease has provided new opportunities for diagnosis, therapy, prevention, and in connecting various domains of medicine. In this article, we overview specific aspects of mitochondrial biology that have contributed to – and likely will continue to enhance the progress of modern medicine.

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Mitochondria: Starving to reach quorum?

Cited by 18 publications

References 31 publications

Mitochondrial morphology transitions and functions: implications for retrograde signaling?

Mitochondrial morphology transitions and functions: implications for retrograde signaling?

What is the function of mitochondrial networks? A theoretical assessment of hypotheses and proposal for future research

The rise of mitochondria in medicine

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