Mitochondrial Proteins Moonlighting in the Nucleus

Monaghan, Richard M.; Whitmarsh, Alan J.

doi:10.1016/j.tibs.2015.10.003

Cited by 89 publications

(73 citation statements)

References 47 publications

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“…It is possible that it is the ΔpH which is involved in part of retrograde signaling through release of mitochondrial proteins which then appear in the nucleus [96]. Mitochondrial retrograde signaling represents communication from mitochondria to the nucleus under both normal and pathological conditions and it serves mitochondria to signal their status to the nucleus and cell.…”

Section: Role Of δψM In Mitochondrial Protein Transport and Retrogradmentioning

confidence: 99%

Mitochondrial membrane potential

Zorova

Popkov

Plotnikov

et al. 2018

Analytical Biochemistry

1,265

910

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The mitochondrial membrane potential (ΔΨm) generated by proton pumps (Complexes I, III and IV) is an essential component in the process of energy storage during oxidative phosphorylation. Together with the proton gradient (ΔpH), ΔΨm forms the transmembrane potential of hydrogen ions which is harnessed to make ATP. The levels of ΔΨm and ATP in the cell are kept relatively stable although there are limited fluctuations of both these factors that can occur reflecting normal physiological activity. However, sustained changes in both factors may be deleterious. A long-lasting drop or rise of ΔΨmvs normal levels may induce unwanted loss of cell viability and be a cause of various pathologies. Among other factors, ΔΨm plays a key role in mitochondrial homeostasis through selective elimination of dysfunctional mitochondria. It is also a driving force for transport of ions (other than H+) and proteins which are necessary for healthy mitochondrial functioning. We propose additional potential mechanisms for which ΔΨm is essential for maintenance of cellular health and viability and provide recommendations how to accurately measure ΔΨm in a cell and discuss potential sources of artifacts.

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Section: Role Of δψM In Mitochondrial Protein Transport and Retrogradmentioning

confidence: 99%

Mitochondrial membrane potential

Zorova

Popkov

Plotnikov

et al. 2018

Analytical Biochemistry

1,265

910

View full text Add to dashboard Cite

show abstract

“…The moonlighting action of several proteins, such as Lys20, Sod1, and Zuo1, takes place in the nucleus. The increasing number of mitochondrial proteins also found in the nucleus suggests that some of them may also have moonlighting roles and participate in regulatory circuits (133). The translocation process of moonlighting proteins has not been studied in detail, except in the case of hexokinase 2, a metabolic enzyme that moonlights as a transcriptional repressor (22).…”

Section: Some Unanswered General Questionsmentioning

confidence: 99%

The Expanding Landscape of Moonlighting Proteins in Yeasts

Gancedo

Flores

Gancedo

2016

Microbiol Mol Biol Rev

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SUMMARYMoonlighting proteins are multifunctional proteins that participate in unrelated biological processes and that are not the result of gene fusion. A certain number of these proteins have been characterized in yeasts, and the easy genetic manipulation of these microorganisms has been useful for a thorough analysis of some cases of moonlighting. As the awareness of the moonlighting phenomenon has increased, a growing number of these proteins are being uncovered. In this review, we present a crop of newly identified moonlighting proteins from yeasts and discuss the experimental evidence that qualifies them to be classified as such. The variety of moonlighting functions encompassed by the proteins considered extends from control of transcription to DNA repair or binding to plasminogen. We also discuss several questions pertaining to the moonlighting condition in general. The cases presented show that yeasts are important organisms to be used as tools to understand different aspects of moonlighting proteins.

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“…Nrf2 is essential for supporting and maintaining normal mitochondrial function and structural integrity, particularly under conditions of cellular/neuronal stress [Dinkova-Kostova and Abramov, 2015;Monaghan and Whitmarsh, 2015] inherent in neurodegenerative disorders [Carrasco-Pozo et al, 2015;Johnson and Johnson, 2015;Denzer et al, 2016]. Dysregulation of histone H3 is common to both neurodevelopmental and neurodegenerative disorders Singh et al, 2015;Kratsman et al, 2016], and hyperacetylation of histone H3 with HDACi increases expression of Nrf2 [Yu et al, 2010;Prasad, 2015].…”

Section: Apoptotic Priming In Mitochondriamentioning

confidence: 99%

Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases

Irwin

Moos

Faller

et al. 2016

Drug Development Research

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Preclinical Research In this review, we discuss epigenetic-driven methods for treating neurodegenerative disorders associated with mitochondrial dysfunction, focusing on carnitinoid antioxidant-histone deacetylase inhibitors that show an ability to reinvigorate synaptic plasticity and protect against neuromotor decline in vivo. Aging remains a major risk factor in patients who progress to dementia, a clinical syndrome typified by decreased mental capacity, including impairments in memory, language skills, and executive function. Energy metabolism and mitochondrial dysfunction are viewed as determinants in the aging process that may afford therapeutic targets for a host of disease conditions, the brain being primary in such thinking. Mitochondrial dysfunction is a core feature in the pathophysiology of both Alzheimer and Parkinson diseases and rare mitochondrial diseases. The potential of new therapies in this area extends to glaucoma and other ophthalmic disorders, migraine, Creutzfeldt-Jakob disease, post-traumatic stress disorder, systemic exertion intolerance disease, and chemotherapy-induced cognitive impairment. An emerging and hopefully more promising approach to addressing these hard-to-treat diseases leverages their sensitivity to activation of master regulators of antioxidant and cytoprotective genes, antioxidant response elements, and mitophagy. Drug Dev Res 77 : 109-123, 2016. © 2016 Wiley Periodicals, Inc.

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Mitochondrial Proteins Moonlighting in the Nucleus

Cited by 89 publications

References 47 publications

Mitochondrial membrane potential

Mitochondrial membrane potential

The Expanding Landscape of Moonlighting Proteins in Yeasts

Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases

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