Partial uncoupling of oxidative phosphorylation induces premature senescence in human fibroblasts and yeast mother cells

Stöckl, Petra; Zankl, Christina; Hütter, Eveline; Unterluggauer, Hermann; Laun, Peter; Heeren, Gino; Bogengruber, Edith; Herndler‐Brandstetter, Dietmar; Breitenbach, Michael; Jansen‐Dürr, Pidder

doi:10.1016/j.freeradbiomed.2007.06.005

Cited by 80 publications

(47 citation statements)

References 58 publications

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“…Thus, it could be reasonably concluded that fungal culture degeneration is linked to cell apoptosis. Nevertheless, in contrast to the aging yeast, Podospora or mammalian cells, which show decreased levels of mt membrane potential (⌬ m ) and ATP production (76,77), the levels of ⌬ m and ATP turnover were higher in sector than the wild type. Provided that there are emerging data with contrary results based on different models of apoptosis and different systems (78,79), the up-regulations of anti-oxidant and antistress enzymes in the sector could contribute to the differences between this study and previous reports on other systems.…”

Section: Discussionmentioning

confidence: 90%

Linkage of Oxidative Stress and Mitochondrial Dysfunctions to Spontaneous Culture Degeneration in Aspergillus nidulans

Lin

Xia

et al. 2014

Molecular & Cellular Proteomics

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Filamentous fungi including mushrooms frequently and spontaneously degenerate during subsequent culture maintenance on artificial media, which shows the loss or reduction abilities of asexual sporulation, sexuality, fruiting, and production of secondary metabolites, thus leading to economic losses during mass production. To better understand the underlying mechanisms of fungal degeneration, the model fungus Aspergillus nidulans was employed in this study for comprehensive analyses. First, linkage of oxidative stress to culture degeneration was evident in A. nidulans. Taken together with the verifications of cell biology and biochemical data, a comparative mitochondrial proteome analysis revealed that, unlike the healthy wild type, a spontaneous fluffy sector culture of A. nidulans demonstrated the characteristics of mitochondrial dysfunctions. Relative to the wild type, the features of cytochrome c release, calcium overload and up-regulation of apoptosis inducing factors evident in sector mitochondria suggested a linkage of fungal degeneration to cell apoptosis. However, the sector culture could still be maintained for generations without the signs of growth arrest. Up-regulation of the heat shock protein chaperones, anti-apoptotic factors and DNA repair proteins in the sector could account for the compromise in cell death. The results of this study not only shed new lights on the mechanisms of spontaneous degeneration of fungal cultures but will also provide alternative biomarkers to monitor fungal culture degeneration. Molecular & Cellular Proteomics

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Section: Discussionmentioning

confidence: 90%

Linkage of Oxidative Stress and Mitochondrial Dysfunctions to Spontaneous Culture Degeneration in Aspergillus nidulans

Lin

Xia

et al. 2014

Molecular & Cellular Proteomics

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“…These are surprising data, because a drop of mitochondrial membrane potential induced by uncouplers such as DNP or FCCP is known to strongly decrease ROS production in isolated mitochondria (27,42,70). However, although it is demonstrated that FCCP reduces ROS production (1), this is not always found in intact cells (8,71,74). If the reasons for these discrepancies are still unclear, Fig.…”

Section: Discussionmentioning

confidence: 99%

Mild mitochondrial uncoupling does not affect mitochondrial biogenesis but downregulates pyruvate carboxylase in adipocytes: role for triglyceride content reduction

Pauw

Demine

Tejerina

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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De Pauw A, Demine S, Tejerina S, Dieu M, Delaive E, Kel A, Renard P, Raes M, Arnould T. Mild mitochondrial uncoupling does not affect mitochondrial biogenesis but downregulates pyruvate carboxylase in adipocytes: role for triglyceride content reduction. Am J Physiol Endocrinol Metab 302: E1123-E1141, 2012. First published February 21, 2012 doi:10.1152/ajpendo.00117.2011In adipocytes, mitochondrial uncoupling is known to trigger a triglyceride loss comparable with the one induced by TNF␣, a proinflammatory cytokine. However, the impact of a mitochondrial uncoupling on the abundance/composition of mitochondria and its connection with triglyceride content in adipocytes is largely unknown. In this work, the effects of a mild mitochondrial uncoupling triggered by FCCP were investigated on the mitochondrial population of 3T3-L1 adipocytes by both quantitative and qualitative approaches. We found that mild mitochondrial uncoupling does not stimulate mitochondrial biogenesis in adipocytes but induces an adaptive cell response characterized by quantitative modifications of mitochondrial protein content. Superoxide anion radical level was increased in mitochondria of both TNF␣-and FCCP-treated adipocytes, whereas mitochondrial DNA copy number was significantly higher only in TNF␣-treated cells. Subproteomic analysis revealed that the abundance of pyruvate carboxylase was reduced significantly in mitochondria of TNF␣-and FCCP-treated adipocytes. Functional study showed that overexpression of this major enzyme of lipid metabolism is able to prevent the triglyceride content reduction in adipocytes exposed to mitochondrial uncoupling or TNF␣. These results suggest a new mechanism by which the effects of mitochondrial uncoupling might limit triglyceride accumulation in adipocytes.adipocytes; carbonyl cyanide p-trifluoromethoxyphenylhydrazone; tumor necrosis factor-␣; mitoproteome OBESITY RESULTS LARGELY FROM A CHRONICALLY POSITIVE energy balance. Therefore, reducing body energy intake and increasing energy expenditure are two approaches that have been translated into strategies to limit fat accumulation. Because mitochondria play a critical role in the process of energy expenditure, the alteration of oxidative phosphorylation (OX-PHOS) efficiency through OXPHOS uncoupling from ATP production in white adipocytes has been considered as an attractive approach to fight obesity (7, 69). In other words, uncoupling increases cellular metabolic demand since uncoupling OXPHOS lowers ATP production and increases the demand for reducing equivalents to restore/maintain mitochondrial membrane potential, thereby increasing substrate catabolism, which would theoretically decrease triglyceride (TG) stores in adipocytes. Indeed, although mitochondrial dysfunction could represent a major cause of lipid metabolism disorders and pathological triglyceride accumulation in several cell lines (50, 75), we and others have shown that mitochondrial uncoupling in adipocytes triggers lipolysis, limits fatty acid synthesis, and leads to a reduction in TG ...

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“…In fact an increase in the ROS production could clearly be observed in senescent cells grown in standard glucose concentration. This increase was related to the mitochondria state [38,39]. During the exponential phase and even more so during ageing, cells grown in CR or SCG displayed small and numerous mitochondria; these differences were previously analysed by Visser [32], who shows that the reticular morphology is associated with a repressed condition typical of growth in high glucose medium or oxygen absence, whereas yeast cells growing on non-fermentable carbon sources display a large number of small mitochondria.…”

Section: Discussionmentioning

confidence: 99%

Different carbon sources affect lifespan and protein redox state during Saccharomyces cerevisiae chronological ageing

Magherini

Carpentieri

Amoresano

et al. 2009

Cell. Mol. Life Sci.

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Abstract. In this study, a proteomic approach that combines selective labelling of proteins containing reduced cysteine residues with two-dimensional electrophoresis/mass spectrometry was used to evaluate the redox state of protein cysteines during chronological ageing in Saccharomyces cerevisiae. The procedure was developed on the grounds that biotinconjugated iodoacetamide (BIAM) specifically reacts with reduced cysteine residues. BIAM-labelled proteins can then be selectively isolated by streptavidin affinity capture. We compared cells grown on 2 % glucose in the exponential phase and during chronological ageing and we found that many proteins undergo cysteine oxidation. The target proteins include enzymes involved in glucose metabolism. Both caloric restriction and growth on glycerol resulted in a decrease in the oxidative modification. Furthermore, in these conditions a reduced production of ROS and a more negative glutathione half cell redox potential were observed.

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Partial uncoupling of oxidative phosphorylation induces premature senescence in human fibroblasts and yeast mother cells

Cited by 80 publications

References 58 publications

Linkage of Oxidative Stress and Mitochondrial Dysfunctions to Spontaneous Culture Degeneration in Aspergillus nidulans

Linkage of Oxidative Stress and Mitochondrial Dysfunctions to Spontaneous Culture Degeneration in Aspergillus nidulans

Mild mitochondrial uncoupling does not affect mitochondrial biogenesis but downregulates pyruvate carboxylase in adipocytes: role for triglyceride content reduction

Different carbon sources affect lifespan and protein redox state during Saccharomyces cerevisiae chronological ageing

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