Exercise and the Regulation of Mitochondrial Turnover

Hood, David A.; Tryon, Liam D.; Vainshtein, Anna; Memme, Jonathan M.; Chen, Christopher; Pauly, Marion; Crilly, Matthew J.; Carter, Heather

doi:10.1016/bs.pmbts.2015.07.007

Cited by 40 publications

(36 citation statements)

References 121 publications

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“…The decreases in these metabolites correlated with disease severity as measured by Karnofsky scores (SI Appendix, Table S1 A-D). Much research has been done on the hypometabolic phenotype in other biologic systems, including dauer (35), diapause (40), hibernation (41), estivation (42), torpor (43), ischemic preconditioning (44), ER stress (45), the unfolded protein response (46), autophagy (47,48), and caloric restriction (49). Dauer, which means persistence or long-lived in German, is an example of one well-studied system.…”

Section: Discussionmentioning

confidence: 99%

Metabolic features of chronic fatigue syndrome

Naviaux

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

311

335

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More than 2 million people in the United States have myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We performed targeted, broad-spectrum metabolomics to gain insights into the biology of CFS. We studied a total of 84 subjects using these methods. Forty-five subjects (n = 22 men and 23 women) met diagnostic criteria for ME/CFS by Institute of Medicine, Canadian, and Fukuda criteria. Thirty-nine subjects (n = 18 men and 21 women) were age- and sex-matched normal controls. Males with CFS were 53 (±2.8) y old (mean ± SEM; range, 21–67 y). Females were 52 (±2.5) y old (range, 20–67 y). The Karnofsky performance scores were 62 (±3.2) for males and 54 (±3.3) for females. We targeted 612 metabolites in plasma from 63 biochemical pathways by hydrophilic interaction liquid chromatography, electrospray ionization, and tandem mass spectrometry in a single-injection method. Patients with CFS showed abnormalities in 20 metabolic pathways. Eighty percent of the diagnostic metabolites were decreased, consistent with a hypometabolic syndrome. Pathway abnormalities included sphingolipid, phospholipid, purine, cholesterol, microbiome, pyrroline-5-carboxylate, riboflavin, branch chain amino acid, peroxisomal, and mitochondrial metabolism. Area under the receiver operator characteristic curve analysis showed diagnostic accuracies of 94% [95% confidence interval (CI), 84–100%] in males using eight metabolites and 96% (95% CI, 86–100%) in females using 13 metabolites. Our data show that despite the heterogeneity of factors leading to CFS, the cellular metabolic response in patients was homogeneous, statistically robust, and chemically similar to the evolutionarily conserved persistence response to environmental stress known as dauer.

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Section: Discussionmentioning

confidence: 99%

Metabolic features of chronic fatigue syndrome

Naviaux

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

311

335

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“…Furthermore, recent emerging evidence shows that mitochondrial loss and dysfunction can mediate disuseinduced skeletal muscle atrophy [10][11][12] . The biological basis and significance of mitochondrial homeostasis in exercised, disuse atrophied, and aged muscles are reviewed in several papers by Hood and colleagues [13][14][15][16][17] .…”

Section: Brief History Of Research On Heat Stress In Skeletal Musclementioning

confidence: 99%

Heat stress induces mitochondrial adaptations in skeletal muscle

Tamura

Hatta

2017

JPFSM

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PURPOSE The purposes of present study were to investigate i) the chronic effects of whole‐body heat stress (WHS) on adaptation of mitochondrial enzyme activity and ii) the acute effects of WHS on kinase phosphorylation known to mediate mitochondrial biogenesis in mice skeletal muscle. METHODS ICR mice were divided into sedentary or WHS group. Mice in WHS group were exposed to hot environment chamber (30 × 20 × 13 cm, ambient temperature: 40 °C) for 30 min on each experiment day. In chronic experiment, we examined the effects of 3 weeks (Frequency: 5 days/week) WHS on maximal citrate synthase (CS) and 3‐Hydroxyacyl‐CoA dehydrogenase (3‐HAD) activities in plantaris muscle. In acute experiment, we studied the effects of a single WHS on phosphorylation of AMP activated protein kinase (AMPK), p38 mitrogen activated protein kinase (p38 MAPK) and calcium/calmodulin‐dependent protein kinase II (CaMK II) in plantaris muscle. RESULTS In chronic experiment, both maximal CS and 3‐HAD activities were increased in WHS group (CS: +35%, P<0.01, 3‐HAD: +49%, P<0.01). In acute experiment, phosphorylation of AMPK in WHS group was decreased (−43%, P<0.05). Phosphorylation of p38 MAPK was increased in WHS group (+252%, P<0.05). Phosphorylation of CaMK II was not different between groups. CONCLUSION Chronic whole‐body heat stress increased mitochondrial enzyme activities.

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“…Exercise elicits many complex physiological responses, including the induction of specific transcription factors such as PGC-1␣ and peroxisome proliferator-activated receptors, which transactivate mitochondrial biogenesis genes (14,15). As a mitochondrial protein import carrier, CHCHD4 is necessary for mitochondrial biogenesis.…”

mentioning

confidence: 99%

Forkhead Box O3A (FOXO3) and the Mitochondrial Disulfide Relay Carrier (CHCHD4) Regulate p53 Protein Nuclear Activity in Response to Exercise

Zhuang

Kamp

et al. 2016

Journal of Biological Chemistry

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Edited by Linda SpremulliAlthough exercise is linked with improved health, the specific molecular mechanisms underlying its various benefits require further clarification. Here we report that exercise increases the nuclear localization and activity of p53 by acutely down-regulating coiled-coil-helix-coiled-coil-helix domain 4 (CHCHD4), a carrier protein that mediates p53 import into the mitochondria. This response to exercise is lost in transgenic mice with constitutive expression of CHCHD4. Mechanistically, exerciseinduced nuclear transcription factor FOXO3 binds to the CHCHD4 promoter and represses its expression, preventing the translocation of p53 to the mitochondria and thereby increasing p53 nuclear localization. The synergistic increase in nuclear p53 and FOXO3 by exercise can facilitate their known interaction in transactivating Sirtuin 1 (SIRT1), a NAD ؉ -dependent histone deacetylase that mediates adaptation to various stresses. Thus, our results reveal one mechanism by which exercise could be involved in preventing cancer and potentially other diseases associated with aging.The nuclear transcriptional activities of p53, well established to play a critical role in tumor suppression, are dynamically regulated by multiple factors, including posttranslational modifications and protein-protein interactions (1-3). Accumulating evidence also shows that p53 localization in non-nuclear subcellular compartments, such as the cytosol and mitochondria, can regulate cellular processes like autophagy and metabolism (4 -6). Although stress-mediated p53 translocation to the mitochondria and its role in cell death have been well delineated, the effect of p53 translocation into mitochondria under normal states is less clear (7,8). Thus, understanding the regulation of p53 partitioning into the mitochondria under physiologic conditions may provide new insights into its tumor-suppressive functions.We reported previously that CHCHD4, 2 the mammalian homolog of the yeast mitochondrial disulfide relay system carrier Mia40, interacts with p53 and mediates its translocation into mitochondria (9). Unlike other mechanisms by which proteins can be imported into mitochondria, the disulfide relay system is coupled to respiration, perhaps reflecting a homeostatic mechanism by which the import of p53 can be regulated by mitochondrial activity (10, 11). Subsequently, p53 import into mitochondria by CHCHD4 facilitates the repair of oxidative mtDNA damage, complementing the nuclear role of p53 in regulating mitochondrial respiration (9, 12, 13). However, these observations also raise questions regarding the physiological significance of the partitioning of p53 between the nucleus and mitochondria and whether such a mechanism can be demonstrated in vivo under normal conditions.Exercise elicits many complex physiological responses, including the induction of specific transcription factors such as PGC-1␣ and peroxisome proliferator-activated receptors, which transactivate mitochondrial biogenesis genes (14, 15). As a mitochondrial protein ...

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Exercise and the Regulation of Mitochondrial Turnover

Cited by 40 publications

References 121 publications

Metabolic features of chronic fatigue syndrome

Metabolic features of chronic fatigue syndrome

Heat stress induces mitochondrial adaptations in skeletal muscle

Forkhead Box O3A (FOXO3) and the Mitochondrial Disulfide Relay Carrier (CHCHD4) Regulate p53 Protein Nuclear Activity in Response to Exercise

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