Exercise modulates liver cellular and mitochondrial proteins related to quality control signaling

Santos‐Alves, Estela; Marques‐Aleixo, Inês; Rizo‐Roca, David; Torrella, Joan Ramón; Oliveira, Paulo J.; Magalhães, José; Ascensão, António

doi:10.1016/j.lfs.2015.06.007

Cited by 53 publications

(33 citation statements)

References 22 publications

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“…Alterations in mitochondrial homeostasis and dynamics have been implicated in aging and age-related disorders (Hara et al, 2014; Zhang et al, 2016) and may also be influenced by exercise training (Santos-alves et al, 2015). Protein levels of DRP1, a protein involved in mitochondrial fission, were significantly increased after exercise training in the cortex of old mice (Figure 6A), while levels of DRP1 were not affected after exercise training in the brains of young mice (Figure 6B).…”

Section: Resultsmentioning

confidence: 99%

“…The relative levels of fission-fusion proteins are known to vary according to body region (Santos-alves et al, 2015). Of note, fission-fusion proteins also varied with duration of exercise, with one study in skeletal muscle showing a decrease in MFN2 levels in skeletal muscle after 45 minutes of exercise with subsequent recovery to levels higher than the pre-exercise baseline (Ding et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

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Exercise increases mitochondrial complex I activity and DRP1 expression in the brains of aged mice

Gusdon

Callio

Distéfano

et al. 2017

Experimental Gerontology

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Exercise is known to have numerous beneficial effects. Recent studies indicate that exercise improves mitochondrial energetics not only in skeletal muscle but also in other tissues. While exercise elicits positive effects on memory, neurogenesis, and synaptic plasticity, the effects of exercise on brain mitochondrial energetics remain relatively unknown. Herein, we studied the effects of exercise training in old and young mice on brain mitochondrial energetics, in comparison to known effects on peripheral tissues that utilize fatty acid oxidation. Exercise improved the capacity for mucle and liver to oxidize palmitate in old mice, but not young mice. In the brain, exercise increased rates of respiration and reactive oxygen species (ROS) production in the old group only while utilizing complex I substrates, effects that were not seen in the young group. Coupled complex I to III enzymatic activity was significantly increased in old trained versus untrained mice with no effect on coupled II to III enzymatic activity. Mitochondrial protein content and markers of mitochondrial biogenesis (PGC-1α and TFAM) were not affected by exercise training in the brain, in contrast to the skeletal muscle of old mice. Brain levels of the autophagy marker LC3-II and protein levels of other signaling proteins that regulate metabolism or transport (BDNF, HSP60, phosphorylated mTOR, FNDC5, SIRT3) were not significantly altered. Old exercised mice showed a significant increase in DRP1 protein levels in the brain without changes in phosphorylation, while MFN2 and OPA1 protein levels were unchanged. Our results suggest that exercise training in old mice can improve brain mitochondrial function through effects on electron transport chain function and mitochondrial dynamics without increasing mitochondrial biogenesis.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Exercise increases mitochondrial complex I activity and DRP1 expression in the brains of aged mice

Gusdon

Callio

Distéfano

et al. 2017

Experimental Gerontology

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“…148 The mechanisms behind these exercise-induced epigenetic changes have not been determined but are likely to involve changes to the mitochondria, including greater ETC activity and mitochondrial turnover. 149–150 …”

Section: Modifiers Of Epigenetic Regulation: Diet Exercise Stresmentioning

confidence: 99%

Wilson disease: At the crossroads between genetics and epigenetics—A review of the evidence

Kieffer

Medici

2017

Liver Research

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Environmental factors, including diet, exercise, stress, and toxins, profoundly impact disease phenotypes. This review examines how Wilson disease (WD), an autosomal recessive genetic disorder, is influenced by genetic and environmental inputs. WD is caused by mutations in the copper-transporter gene ATP7B, leading to the accumulation of copper in the liver and brain, resulting in hepatic, neurological, and psychiatric symptoms. These symptoms range in severity and can first appear anytime between early childhood and old age. Over 300 disease-causing mutations in ATP7B have been identified, but attempts to link genotype to the phenotypic presentation have yielded little insight, prompting investigators to identify alternative mechanisms, such as epigenetics, to explain the highly varied clinical presentation. Further, WD is accompanied by structural and functional abnormalities in mitochondria, potentially altering the production of metabolites that are required for epigenetic regulation of gene expression. Notably, environmental exposure affects the regulation of gene expression and mitochondrial function. We present the “multi-hit” hypothesis of WD progression, which posits that the initial hit is an environmental factor that affects fetal gene expression and epigenetic mechanisms and subsequent “hits” are environmental exposures that occur in the offspring after birth. These environmental hits and subsequent changes in epigenetic regulation may impact copper accumulation and ultimately WD phenotype. Lifestyle changes, including diet, increased physical activity, stress reduction, and toxin avoidance, might influence the presentation and course of WD, and therefore may serve as potential adjunctive or replacement therapies.

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“…In addition to chemical compounds, lifestyle interventions also affect p66Shc expression/activity. Caloric restriction, fasting (Giorgio et al , ) and exercise (Santos‐Alves et al , ) were reported to reduce p66Shc gene expression and p66Shc (serine 36) phosphorylation in mouse liver, fat and muscle. In contrast, cold exposure or obesogenic high fat diet increase p66Shc protein levels in mouse fat and muscle (Berniakovich et al , ; Tomilov et al , ; Giorgio et al , ).…”

Section: Therapeutic Potential Of P66shc Inhibitionmentioning

confidence: 99%

New aspects of p66Shc in ischaemia reperfusion injury and other cardiovascular diseases

Lisa

Giorgio

Ferdinándy

et al. 2016

British J Pharmacology

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Although reactive oxygen species (ROS) act as crucial factors in the onset and progression of a wide array of diseases, they are also involved in numerous signalling pathways related to cell metabolism, growth and survival. ROS are produced at various cellular sites, and it is generally agreed that mitochondria generate the largest amount, especially those in cardiomyocytes. However, the identification of the most relevant sites within mitochondria, the interaction among the various sources, and the events responsible for the increase in ROS formation under pathological conditions are still highly debated, and far from being clarified. Here, we review the information linking the adaptor protein p66Shc with cardiac injury induced by ischaemia and reperfusion (I/ R), including the contribution of risk factors, such as metabolic syndrome and ageing. In response to several stimuli, p66Shc migrates into mitochondria where it catalyses electron transfer from cytochrome c to oxygen resulting in hydrogen peroxide formation. Deletion of p66Shc has been shown to reduce I/R injury as well as vascular abnormalities associated with diabetes and ageing. However, p66Shc-induced ROS formation is also involved in insulin signalling and might contribute to self-endogenous defenses against mild I/R injury. In addition to its role in physiological and pathological conditions, we discuss compounds and conditions that can modulate the expression and activity of p66Shc. LINKED ARTICLESThis article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc Abbreviations ATG, DNA codon for methionine; CAD, coronary artery disease; CH, collagen homologues; Δψ m , mitochondrial membrane potential; ETC, electron transport chain; GSH/GSSG, GSH in its reduced or oxidized form; IGF-1, insulin-like growth factor 1; PTP, permeability transition pore; PBM, peripheral blood monocyte; Ras, rat sarcoma; SH2, sarcoma homologous type 2; Sirtuin, silent mating type information regulation 2 homolog Cardiac injury induced by ischaemia and reperfusionThe maintenance of cardiac structure and function depends on the continuous supply of ATP resulting from the mitochondrial coupling of substrate oxidation with ATP synthesis, termed as oxidative phosphorylation. The strict dependence of the heart on aerobic metabolism is indicated by the large fraction (i.e. >30%) of cardiomyocyte volume occupied by mitochondria. Therefore, it is hardly surprising that mitochondrial dysfunction and cardiac diseases are inevitably associated. This concept is perfectly exemplified by cardiac injury induced by ischaemia and reperfusion. Because more than 95% of oxygen is utilized by the terminal reaction of the respiratory chain, namely, cytochrome oxidase, anoxia or ischaemia is established when oxygen availability is no longer sufficient for the activity of cytochrome oxidase. Therefore, within any cell, ischaemic injury is determined...

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Exercise modulates liver cellular and mitochondrial proteins related to quality control signaling

Cited by 53 publications

References 22 publications

Exercise increases mitochondrial complex I activity and DRP1 expression in the brains of aged mice

Exercise increases mitochondrial complex I activity and DRP1 expression in the brains of aged mice

Wilson disease: At the crossroads between genetics and epigenetics—A review of the evidence

New aspects of p66Shc in ischaemia reperfusion injury and other cardiovascular diseases

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