Mitochondrial wrinkles: the first signs of ageing?

Raftopoulou, Myrto

doi:10.1038/ncb0905-853

Cited by 5 publications

(3 citation statements)

References 1 publication

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“…Apoptosis and aging has been extensively associated with enhanced ROS production 61626364. Thus, the improvement of mitochondrial function and/or antioxidant defenses may decrease mitochondrial ROS production or increase its detoxification, leading to CLS extension.…”

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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“…Depending on the type of the stimulus, autophagy can function as a cell survival or a cell death mechanism [11,35,36]. To evaluate the role of GA-DM in the induction autophagy, we conducted a post-treatment timeline western blotting to analyze changes in autophagic protein Beclin-1 that has long been identified as a Bcl-2-interacting partner [35,37,38]. Results showed a significant increase in Beclin-1 protein expression at 3-6 h after GA-DM treatment, which was drastically declined after 12 h of treatment ( Figure 5A, B).…”

Section: Ga-dm Treatment Induces Cross-talk Between Autophagy and Apomentioning

confidence: 99%

A possible cross-talk between autophagy and apoptosis in generating an immune response in melanoma

et al. 2012

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Melanoma is the most aggressive form of skin cancer, responsible for the majority of skin cancer related deaths. Thus, the search for natural molecules which can effectively destroy tumors while promoting immune activation is essential for designing novel therapies against metastatic melanoma. Here, we report for the first time that a natural triterpenoid, Ganoderic Acid DM (GA-DM), induces an orchestrated autophagic and apoptotic cell death, as well as enhanced immunological responses via increased HLA class II presentation in melanoma cells. Annexin V staining and flow cytometry showed that GA-DM treatment induced apoptosis of melanoma cells, which was supported by a detection of increased Bax proteins, co-localization and elevation of Apaf-1 and cytochrome c, and a subsequent cleavage of caspases 9 and 3. Furthermore, GA-DM treatment initiated a possible cross-talk between autophagy and apoptosis as evidenced by increased levels of Beclin-1 and LC3 proteins, and their timely interplay with apoptotic and/or anti-apoptotic molecules in melanoma cells. Despite GA-DM's moderate cytotoxicity, viable cells expressed high levels of HLA class II proteins with improved antigen presentation and CD4+ T cell recognition. The antitumor efficacy of GA-DM was also investigated in vivo in murine B16 melanoma model, where GA-DM treatment slowed tumor formation with a significant reduction in tumor volume. Taken together, these findings demonstrate the potential of GA-DM as a natural chemo-immunotherapeutic capable of inducing a possible cross-talk between autophagy and apoptosis, as well as improved immune recognition for sustained melanoma tumor clearance.

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“…The causative role of mitochondrial dysfunction in the ageing process of the somatic cells has been known from several studies [135][136][137][138][139]. This is mainly through the damage incurred by reactive oxygen species (ROS) to the mitochondrial DNA and the subsequent abnormalities in oxidative metabolism and ATP production, which affects almost every aspect of cellular function, including replication [140][141][142].…”

Section: Menopausementioning

confidence: 99%

Reproductive ageing in women

Djahanbakhch

Ezzati

Zosmer

2007

The Journal of Pathology

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The traditional view in respect to female reproduction is that the number of oocytes at birth is fixed and continuously declines towards the point when no more oocytes are available after menopause. In this review we briefly discuss the embryonic development of female germ cells and ovarian follicles. The ontogeny of the hypothalamic-pituitary-gonadal axis is then discussed, with a focus on pubertal transition and normal ovulatory menstrual cycles during female adult life. Biochemical markers of menopausal transition are briefly examined. We also examine the effects of age on female fertility, the contribution of chromosomal abnormalities of the oocyte to the observed decline in female fertility with age and the possible biological basis for the occurrence of such abnormalities. Finally, we consider the effects of maternal age on obstetric complications and perinatal outcome. New data that have the potential to revolutionize our understanding of mammalian oogenesis and follicular formation, and of the female reproductive ageing process, are also briefly considered.

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Mitochondrial wrinkles: the first signs of ageing?

Cited by 5 publications

References 1 publication

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

A possible cross-talk between autophagy and apoptosis in generating an immune response in melanoma

Reproductive ageing in women

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