Differences in Mitochondrial Coupling Reveal a Novel Signature of Mitohormesis in Muscle of Healthy Individuals

Sparks, Lauren M.; Redman, Leanne M.; Conley, Kevin E.; Harper, Mary‐Ellen; Hodges, Andrew; Eroshkin, Alexey; Costford, Sheila R.; Gabriel, Meghan E.; Yi, Fanchao; Shook, Cherie; Cornnell, Heather H.; Ravussin, Éric; Smith, Steven R.

doi:10.1210/jc.2016-2742

Cited by 6 publications

(5 citation statements)

References 39 publications

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“…3A ). To ensure equal loading for all samples total protein level in each sample was determined on PVDF membranes by staining with REVERT, a validated method for normalization of Western blots 39 – 41 . The Li-COR Odyssey software was employed to quantify the amount of proteins in each sample on the REVERT stained membranes and we used these values to normalize the amount of SMA, calponin, caldesmon and E-cadherin staining obtained by Western blotting.…”

Section: Resultsmentioning

confidence: 99%

Myoepithelial cell-driven acini contraction in response to oxytocin receptor stimulation is impaired in lacrimal glands of Sjögren’s syndrome animal models

Hawley

Tang

Zyrianova

et al. 2018

Sci Rep

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The purpose of the present studies was to investigate the impact of chronic inflammation of the lacrimal gland, as occurs in Sjögren’s syndrome, on the morphology and function of myoepithelial cells (MECs). In spite of the importance of MECs for lacrimal gland function, the effect of inflammation on MECs has not been well defined. We studied changes in MEC structure and function in two animal models of aqueous deficient dry eye, NOD and MRL/lpr mice. We found a statistically significant reduction in the size of MECs in diseased compared to control lacrimal glands. We also found that oxytocin receptor was highly expressed in MECs of mouse and human lacrimal glands and that its expression was strongly reduced in diseased glands. Furthermore, we found a significant decrease in the amount of two MEC contractile proteins, α-smooth muscle actin (SMA) and calponin. Finally, oxytocin-mediated contraction was impaired in lacrimal gland acini from diseased glands. We conclude that chronic inflammation of the lacrimal gland leads to a substantial thinning of MECs, down-regulation of contractile proteins and oxytocin receptor expression, and therefore impaired acini contraction. This is the first study highlighting the role of oxytocin mediated MEC contraction on lacrimal gland function.

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Section: Resultsmentioning

confidence: 99%

Myoepithelial cell-driven acini contraction in response to oxytocin receptor stimulation is impaired in lacrimal glands of Sjögren’s syndrome animal models

Hawley

Tang

Zyrianova

et al. 2018

Sci Rep

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“…This counterintuitive example illustrates the complexity of mitochondrial biology, as reduced mitochondrial function can, in some cases, induce a protective response through a process referred to as mitohormesis [44]. Although the precise mechanisms underlying this protective response remain unclear and somewhat controversial [45,46], examples of mitohormesis-associated lifespan extension have been observed in budding yeast [47,48], nematode worms [49,50], fruit flies [51], and mice [51][52][53], with suggestive evidence for such a mechanism in humans as well [54]. It is worth also noting, however, that a mouse model with deficient respiration was neither long-lived nor short-lived and had no obvious deleterious phenotypes [55].…”

Section: Pmf and Agingmentioning

confidence: 92%

An energetics perspective on geroscience: mitochondrial protonmotive force and aging

Berry

Kaeberlein

2021

GeroScience

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Mitochondria are organelles that provide energy to cells through ATP production. Mitochondrial dysfunction has long been postulated to mediate cellular declines that drive biological aging. Many wellcharacterized hallmarks of aging may involve underlying energetic defects that stem from loss of mitochondrial function with age. Why and how mitochondrial function declines with age is an open question and one that has been difficult to answer. Mitochondria are powered by an electrochemical gradient across the inner mitochondrial membrane known as the protonmotive force (PMF). This gradient decreases with age in several experimental models. However, it is unclear if a diminished PMF is a cause or a consequence of aging. Herein, we briefly review and define mitochondrial function, we summarize how PMF changes with age in several models, and we highlight recent studies that implicate PMF in aging biology. We also identify barriers that must be addressed for the field to progress. Emerging technology permits more precise in vivo study of mitochondria that will allow better understanding of cause and effect in metabolic models of aging. Once cause and effect can be discerned more precisely, energetics approaches to combat aging may be developed to prevent or reverse functional decline.

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“…Studies have demonstrated extensive variation in mitochondrial coupling measured in vivo in human muscle (50,51) (Figure 3). These studies and others suggest that this variation might contribute to the reduced EE and propensity to regain weight in the weight‐reduced state.…”

Section: Potential Mechanisms For Metabolic Adaptation In the Weight‐mentioning

confidence: 99%

Physiology of Energy Expenditure in the Weight‐Reduced State

Ravussin

Smith

Ferrante

2021

Obesity

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Although many individuals achieve weight loss of 10% or more, the ability to maintain a reduced body mass over months and years is much rarer. Unfortunately, our understanding of the adverse consequences of having overweight and obesity argues that long‐term maintenance of a reduced weight provides the greatest health benefit. However, to achieve long‐term weight reduction requires overcoming neuroendocrine systems that favor restoration of one’s initial weight. Identifying and characterizing the components of these systems will be important if we are to develop therapies and strategies to reduce the rates of obesity and its complications in our modern society. During this session, Eric Ravussin and Steven R. Smith, respectively, discussed the physiology of the weight‐reduced state that favors weight regain and a molecular component that contributes to this response.

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Differences in Mitochondrial Coupling Reveal a Novel Signature of Mitohormesis in Muscle of Healthy Individuals

Abstract: Higher muscle mitochondrial coupling is accompanied by an overall elevation in mitochondrial function, a novel transcriptional signature of oxidative stress and mitochondrial remodeling and indications of an mitochondrial unfolded protein response.

Cited by 6 publications

References 39 publications

Myoepithelial cell-driven acini contraction in response to oxytocin receptor stimulation is impaired in lacrimal glands of Sjögren’s syndrome animal models

Myoepithelial cell-driven acini contraction in response to oxytocin receptor stimulation is impaired in lacrimal glands of Sjögren’s syndrome animal models

An energetics perspective on geroscience: mitochondrial protonmotive force and aging

Physiology of Energy Expenditure in the Weight‐Reduced State

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