Maintenance of Mitochondrial Morphology by Autophagy and Its Role in High Glucose Effects on Chronological Lifespan of<i>Saccharomyces cerevisiae</i>

Aung-Htut, May T.; Lam, Yuen Ting; Lim, Yu-Leng; Rinnerthaler, Mark; Gelling, Cristy; Yang, Hongyuan; Breitenbach, Michael; Dawes, Ian W.

doi:10.1155/2013/636287

Cited by 16 publications

(10 citation statements)

References 46 publications

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“…Previous studies have demonstrated that autophagy has an important role in maintaining proper mitochondrial function and dynamics since autophagy-defective mutants present severe mitochondria dysfunctions 57 58 . In particular, the regulation of the mitochondrial membrane potential appears to be crucial to regulate autophagic flux.…”

Section: Resultsmentioning

confidence: 99%

Reduced TORC1 signaling abolishes mitochondrial dysfunctions and shortened chronological lifespan of Isc1p-deficient cells

Teixeira¹,

Medeiros²,

Vilaça³

et al. 2014

MIC

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The target of rapamycin (TOR) is an important signaling pathway on a hierarchical network of interacting pathways regulating central biological processes, such as cell growth, stress response and aging. Several lines of evidence suggest a functional link between TOR signaling and sphingolipid metabolism. Here, we report that the TORC1-Sch9p pathway is activated in cells lacking Isc1p, the yeast orthologue of mammalian neutral sphingomyelinase 2. The deletion of TOR1 or SCH9 abolishes the premature aging, oxidative stress sensitivity and mitochondrial dysfunctions displayed by isc1Δ cells and this is correlated with the suppression of the autophagic flux defect exhibited by the mutant strain. The protective effect of TOR1 deletion, as opposed to that of SCH9 deletion, is not associated with the attenuation of Hog1p hyperphosphorylation, which was previously implicated in isc1Δ phenotypes. Our data support a model in which Isc1p regulates mitochondrial function and chronological lifespan in yeast through the TORC1-Sch9p pathway although Isc1p and TORC1 also seem to act through independent pathways, as isc1Δtor1Δ phenotypes are intermediate to those displayed by isc1Δ and tor1Δ cells. We also provide evidence that TORC1 downstream effectors, the type 2A protein phosphatase Sit4p and the AGC protein kinase Sch9p, integrate nutrient and stress signals from TORC1 with ceramide signaling derived from Isc1p to regulate mitochondrial function and lifespan in yeast. Overall, our results show that TORC1-Sch9p axis is deregulated in Isc1p-deficient cells, contributing to mitochondrial dysfunction, enhanced oxidative stress sensitivity and premature aging of isc1Δ cells.

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Section: Resultsmentioning

confidence: 99%

Reduced TORC1 signaling abolishes mitochondrial dysfunctions and shortened chronological lifespan of Isc1p-deficient cells

Teixeira¹,

Medeiros²,

Vilaça³

et al. 2014

MIC

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“…Since mitochondria are both the targets for oxidative stress and as a rich source of ROS (Burtner et al 2009; Aung-Htut et al 2013), we hypothesized that mitochondrial dysfunction could be involved in arsenic nephrotoxicity. We found that arsenic exposure led to altered mitochondrial morphology (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Tetramethylpyrazine (TMP) protects against sodium arsenite-induced nephrotoxicity by suppressing ROS production, mitochondrial dysfunction, pro-inflammatory signaling pathways and programed cell death

et al. 2014

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Although kidney is a target organ of arsenic cytotoxicity, the underlying mechanisms of arsenic-induced nephrotoxicity remain poorly understood. As tetramethylpyrazine (TMP) has recently been found to be a renal protectant in multiple kidney injuries, we hypothesize that TMP could suppress arsenic nephrotoxicity. In this study, human renal proximal tubular epithelial cell line HK-2 was used to elucidate the precise mechanisms of arsenic nephrotoxicity as well as the protective mechanism of TMP in these cells. Sodium arsenite exposure dramatically increased cellular reactive oxygen species (ROS) production, decreased levels of cellular glutathione (GSH), decreased cytochrome c oxidase activity and mitochondrial membrane potential, which indicated mitochondrial dysfunction. On the other hand, sodium arsenite activated pro-inflammatory signals, including β-catenin, nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (MAPK), tumor necrosis factor alpha and cyclooxygenase-2 (COX-2). Small molecule inhibitors of NF-κB and p38 MAPK blocked arsenic-induced COX-2 expression, suggesting arsenic-induced COX-2 upregulation was NF-κB- and p38 MAPK-dependent. Finally, sodium arsenite induced autophagy in HK-2 cells at early phase (6 h) and the subsequent apoptosis at 24 h. Treatment by TMP or by the antioxidant N-acetylcysteine decreased arsenic-induced ROS production, enhanced GSH levels, prevented mitochondria dysfunction and suppressed the activation of pro-inflammatory signals and the development of autophagy and apoptosis. Our results suggested that TMP may be used as a new potential therapeutic agent to prevent arsenic-induced nephrotoxicity by suppressing these pathological processes.

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“…The contribution of mitochondria to the production of ROS in the skin is only substantial in the stem cells, but further on is small compared to other organs, because during the cornification process the keratinocytes degrade all their organelles including the nucleus, mitochondria, peroxisomes, and the endoplasmic reticulum [ 80 , 81 ]. The importance of mitochondria in the aging process independently of the production of ROS is summarized elsewhere [ 82 , 83 , 84 ].…”

Section: Ros Production In the Skinmentioning

confidence: 99%

Oxidative Stress in Aging Human Skin

et al. 2015

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Oxidative stress in skin plays a major role in the aging process. This is true for intrinsic aging and even more for extrinsic aging. Although the results are quite different in dermis and epidermis, extrinsic aging is driven to a large extent by oxidative stress caused by UV irradiation. In this review the overall effects of oxidative stress are discussed as well as the sources of ROS including the mitochondrial ETC, peroxisomal and ER localized proteins, the Fenton reaction, and such enzymes as cyclooxygenases, lipoxygenases, xanthine oxidases, and NADPH oxidases. Furthermore, the defense mechanisms against oxidative stress ranging from enzymes like superoxide dismutases, catalases, peroxiredoxins, and GSH peroxidases to organic compounds such as L-ascorbate, Į-tocopherol, beta-carotene, uric acid, CoQ10, and glutathione are described in more detail. In addition the oxidative stress induced modifications caused to proteins, lipids and DNA are discussed. Finally age-related changes of the skin are also a topic of this review. They include a disruption of the epidermal calcium gradient in old skin with an accompanying change in the composition of the cornified envelope. This modified cornified envelope also leads to an altered anti-oxidative capacity and a reduced barrier function of the epidermis.

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Maintenance of Mitochondrial Morphology by Autophagy and Its Role in High Glucose Effects on Chronological Lifespan ofSaccharomyces cerevisiae

Cited by 16 publications

References 46 publications

Reduced TORC1 signaling abolishes mitochondrial dysfunctions and shortened chronological lifespan of Isc1p-deficient cells

Reduced TORC1 signaling abolishes mitochondrial dysfunctions and shortened chronological lifespan of Isc1p-deficient cells

Tetramethylpyrazine (TMP) protects against sodium arsenite-induced nephrotoxicity by suppressing ROS production, mitochondrial dysfunction, pro-inflammatory signaling pathways and programed cell death

Oxidative Stress in Aging Human Skin

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