Mitochondrial synapses: intracellular communication and signal integration

Picard, Martin

doi:10.1016/j.tins.2015.06.001

Cited by 47 publications

(43 citation statements)

References 77 publications

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“…But in complex multicellular organisms, function must be matched to the available supply of energy – a cell should only attempt to divide if there are sufficient levels of the right energy substrates. Given the role of mitochondria in evolution of complex life forms, it is logical that a cell’s gene expression, and in particular basic cellular operations such as cell division, growth, and size regulation (Picard et al, 2014), and even cell death, would be coupled to mitochondrial metabolic signals (Chandel, 2015; Kasahara and Scorrano, 2014; Picard, 2015). …”

Section: Energy Is Required For Life and Stress Adaptationmentioning

confidence: 99%

“…Moreover, in addition to the shared chemical “language” between mitochondria and the epigenome, mitochondria are in close physical proximity to the nucleus and nuclear pores where molecular information transit in and out of the nucleus (Picard, 2015). This presumably facilitates the diffusion of metabolic signals that reflect the integrated state of mitochondrial metabolism to the epigenetic machinery.…”

Section: Energy Is Required For Life and Stress Adaptationmentioning

confidence: 99%

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An energetic view of stress: Focus on mitochondria

Picard

McEwen

Epel

et al. 2018

Frontiers in Neuroendocrinology

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402

309

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Energy is required to sustain life and enable stress adaptation. At the cellular level, energy is largely derived from mitochondria – unique multifunctional organelles with their own genome. Four main elements connect mitochondria to stress: (1) Energy is required at the molecular, (epi)genetic, cellular, organellar, and systemic levels to sustain components of stress responses; (2) Glucocorticoids and other steroid hormones are produced and metabolized by mitochondria; (3) Reciprocally, mitochondria respond to neuroendocrine and metabolic stress mediators; and (4) Experimentally manipulating mitochondrial functions alters physiological and behavioral responses to psychological stress. Thus, mitochondria are endocrine organelles that provide both the energy and signals that enable and direct stress adaptation. Neural circuits regulating social behavior – as well as psychopathological processes – are also influenced by mitochondrial energetics. An integrative view of stress as an energy-driven process opens new opportunities to study mechanisms of adaptation and regulation across the lifespan.

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Section: Energy Is Required For Life and Stress Adaptationmentioning

confidence: 99%

Section: Energy Is Required For Life and Stress Adaptationmentioning

confidence: 99%

An energetic view of stress: Focus on mitochondria

Picard

McEwen

Epel

et al. 2018

Frontiers in Neuroendocrinology

Self Cite

402

309

View full text Add to dashboard Cite

show abstract

“…For example, synaptic transmission requires mitochondrial ATP generation and control of local [Ca2+] levels for neurotransmitter exocytosis, and potentiation of neurotransmitter release (Picard, 2015). Moreover, it is becoming well-recognized that mitochondrial dysfunction plays an important role in the pathophysiology of several major psychiatric disorders, while mitochondrial fragmentation has been shown to be one of the hallmarks of neurodegeneration (Lin and Beal, 2006).…”

Section: Introductionmentioning

confidence: 99%

A heterogeneous population of nuclear-encoded mitochondrial mRNAs is present in the axons of primary sympathetic neurons

et al. 2016

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Mitochondria are enriched in subcellular regions of high energy consumption, such as axons and pre-synaptic nerve endings. Accumulating evidence suggests that mitochondrial maintenance in these distal structural/functional domains of the neuron depends on the “in-situ” translation of nuclear-encoded mitochondrial mRNAs. In support of this notion, we recently provided evidence for the axonal targeting of several nuclear-encoded mRNAs, such as cytochrome c oxidase, subunit 4 (COXIV), ATP synthase, H+ transporting and mitochondrial Fo complex, subunit C1 (ATP5G1). Furthermore, we showed that axonal trafficking and local translation of these mRNAs plays a critical role in the generation of axonal ATP. Using a global gene expression analysis, this study identified a highly diverse population of nuclear-encoded mRNAs that were enriched in the axon and presynaptic nerve terminals. Among this population of mRNAs, fifty seven were found to be at least two fold more abundant in distal axons, as compared with the parental cell bodies. Gene ontology analysis of the nuclear-encoded mitochondrial mRNAs suggested functions for these gene products in molecular and biological processes, including but not limited to oxidoreductase and electron carrier activity and proton transport. Based on these results, we postulate that local translation of nuclear-encoded mitochondrial mRNAs present in the axons may play an essential role in local energy production and maintenance of mitochondrial function.

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“…While most attention is given to the synaptic mitochondria required to supply the estimated 4.7 billion ATP molecules per second of a single neuron's activity [ 129 ], mitochondria within the cell body are also critical for neuronal function via retrograde signaling. In the soma, mitochondria are positioned in the perinuclear region, in close proximity to the chromatin [ 130 ]. The chromatin is the DNA-protein structure that modulates gene accessibility by either "closing" portions of the genome to repress transcription or "opening" them to promote their expression.…”

Section: Metabolic Signaling and The Epigenetic Languagementioning

confidence: 99%

“…Mitochondrial regulation of gene expression is facilitated by two major factors. The fi rst is "topological," consisting in the perinuclear positioning of mitochondria only a few hundred nanometers away from the nuclear pores through which molecular signals travel [ 130 ]. The second and more studied factor that enables mitochondria-nuclear signaling is the nature of biochemical signals that induce epigenetic modifi cations, most of which are produced by mitochondria.…”

Section: Metabolic Signaling and The Epigenetic Languagementioning

confidence: 99%

Mitochondrial Signaling and Neurodegeneration

Picard

McManus

2016

Mitochondrial Dysfunction in Neurodegenerative Disorders

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The endosymbiosis of mitochondria and the resulting increase in energy supply thus conferred upon the eukaryotic cell enabled the evolution of multicellular organisms and complex organs, such as the brain. As a result, the brain and other organs with high energy demands, depend heavily upon mitochondrial metabolism for normal function, and as a consequence, defects in mitochondrial function lead to neurodegenerative disorders. However, the mechanisms linking mitochondrial defects to hallmarks of neurodegeneration, such as the protein aggregates are also extracellular epigenetic alterations, abnormal gene expression, systemic infl ammation, and protein aggregates, remain unclear.Emerging evidence demonstrates that mitochondria are not only power-generating organelles, but also engage in signaling at multiple levels. During the bioenergetic decline associated with aging, dysfunctional mitochondria generate signals of stress (SOS) that can trigger and/or amplify neurodegenerative processes. In this chapter, we describe emerging mechanisms for mitochondrial signaling at four different levels. Mitochondria communicate (1) with each other via fusion and specialized inter-mitochondrial junctions, (2) with cytoplasmic components via posttranslational modifi cations that shift signaling pathways and promote protein aggregation, (3) with the nucleus to regulate epigenetic modifi cations and gene expression, and (4) with the systemic environment where they alter neuroendocrine and infl ammatory processes that impact neuronal function. The relevance of mitochondrial signaling to neurodegeneration is discussed.

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Mitochondrial synapses: intracellular communication and signal integration

Cited by 47 publications

References 77 publications

An energetic view of stress: Focus on mitochondria

An energetic view of stress: Focus on mitochondria

A heterogeneous population of nuclear-encoded mitochondrial mRNAs is present in the axons of primary sympathetic neurons

Mitochondrial Signaling and Neurodegeneration

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