Going nuclear with stress

Wong, Wei

doi:10.1126/scisignal.aav4285

Cited by 5 publications

(2 citation statements)

References 2 publications

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“…It acts as a regulator of metabolic homeostasis that can prevent diet-induced obesity and insulin resistance, and age-dependent insulin resistance in mice (99–101). Notably, MOTS-c can translocate to the nucleus upon cellular stress to regulate adaptive nuclear gene expression by interacting with other stress-responsive transcription factors including nuclear factor erythroid 2-related factor 2 (NFE2L2/NRF2) and binding to chromatin (102–104). HEK293 cells that over-express MOTS-c were significantly protected against metabolic stress ( i.e ., glucose and serum deprivation) (102).…”

Section: Cell-autonomous Mitochondrial Communication and Agingmentioning

confidence: 99%

Mitochondria: multifaceted regulators of aging

Son

Lee

2019

BMB Rep.

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Aging is accompanied by a time-dependent progressive deterioration of multiple factors of the cellular system. The past several decades have witnessed major leaps in our understanding of the biological mechanisms of aging using dietary, genetic, pharmacological, and physical interventions. Metabolic processes, including nutrient sensing pathways and mitochondrial function, have emerged as prominent regulators of aging. Mitochondria have been considered to play a key role largely due to their production of reactive oxygen species (ROS), resulting in DNA damage that accumulates over time and ultimately causes cellular failure. This theory, known as the mitochondrial free radical theory of aging (MFRTA), was favored by the aging field, but increasing inconsistent evidence has led to criticism and rejection of this idea. However, MFRTA should not be hastily rejected in its entirety because we now understand that ROS is not simply an undesired toxic metabolic byproduct, but also an important signaling molecule that is vital to cellular fitness. Notably, mitochondrial function, a term traditionally referred to bioenergetics and apoptosis, has since expanded considerably. It encompasses numerous other key biological processes, including the following: (i) complex metabolic processes, (ii) intracellular and endocrine signaling/communication, and (iii) immunity/inflammation. Here, we will discuss shortcomings of previous concepts regarding mitochondria in aging and their emerging roles based on recent advances. We will also discuss how the mitochondrial genome integrates with major theories on the evolution of aging.

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Section: Cell-autonomous Mitochondrial Communication and Agingmentioning

confidence: 99%

Mitochondria: multifaceted regulators of aging

Son

Lee

2019

BMB Rep.

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“…[6,8] We have recently reported that one particular MDP, MOTS-c (mitochondrial open reading frame of the 12S ribosomal RNA type-c), can translocate to the nucleus to regulate adaptive gene expression in response to cellular stress. [9][10][11][12] Here, we discuss the implications of MOTS-c, a mitochondrial-encoded regulator of the nuclear genome, and propose that the dual mitonuclear genomes should be considered a singular genetic system that is coordinated through dynamic intergenomic communication using reciprocal gene-encoded regulators. We suggest a more inclusive approach to gene network analyses for basic research and therapeutic development.…”

Section: Introductionmentioning

confidence: 99%

MOTS‐c: A Mitochondrial‐Encoded Regulator of the Nucleus

Benayoun

Lee

2019

BioEssays

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Mitochondria are increasingly being recognized as information hubs that sense cellular changes and transmit messages to other cellular components, such as the nucleus, the endoplasmic reticulum (ER), the Golgi apparatus, and lysosomes. Nonetheless, the interaction between mitochondria and the nucleus is of special interest because they both host part of the cellular genome. Thus, the communication between genome‐bearing organelles would likely include gene expression regulation. Multiple nuclear‐encoded proteins have been known to regulate mitochondrial gene expression. On the contrary, no mitochondrial‐encoded factors are known to actively regulate nuclear gene expression. MOTS‐c (mitochondrial open reading frame of the 12S ribosomal RNA type‐c) is a recently identified peptide encoded within the mitochondrial 12S ribosomal RNA gene that has metabolic functions. Notably, MOTS‐c can translocate to the nucleus upon metabolic stress (e.g., glucose restriction and oxidative stress) and directly regulate adaptive nuclear gene expression to promote cellular homeostasis. It is hypothesized that cellular fitness requires the coevolved mitonuclear genomes to coordinate adaptive responses using gene‐encoded factors that cross‐regulate the opposite genome. This suggests that cellular gene expression requires the bipartite split genomes to operate as a unified system, rather than the nucleus being the sole master regulator.

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