Ceramide signalling impinges on Sit4p and Hog1p to promote mitochondrial fission and mitophagy in Isc1p-deficient cells

Teixeira, Vítor; Medeiros, Tania; Vilaça, Rita; Pereira, Andreia; Chaves, Susana R.; Côrte‐Real, Manuela; Moradas‐Ferreira, Pedro; Costa, Vítor Santos

doi:10.1016/j.cellsig.2015.06.001

Cited by 27 publications

(24 citation statements)

References 46 publications

(79 reference statements)

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“…Twig et al, 2008;Wei et al, 2015). In yeast, mitophagy induced by the deletion of phosphosphingolipid phospholipase gene ISC1 requires the dynamin-related protein Dnm1p, the key component of the mitochondrial fission machinery (Teixeira et al, 2015). However, the well studied starvation-induced mechanisms of autophagic mitochondria degradation do not require mitochondrial fission and are not sensitive to uncoupling (Mendl et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial depolarization in yeast zygotes inhibits clonal expansion of selfish mtDNA

Karavaeva

Golyshev

Смирнова

et al. 2017

Journal of Cell Science

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Non-identical copies of mitochondrial DNA (mtDNA) compete with each other within a cell and the ultimate variant of mtDNA present depends on their relative replication rates. Using yeast Saccharomyces cerevisiae cells as a model, we studied the effects of mitochondrial inhibitors on the competition between wild-type mtDNA and mutant selfish mtDNA in heteroplasmic zygotes. We found that decreasing mitochondrial transmembrane potential by adding uncouplers or valinomycin changes the competition outcomes in favor of the wild-type mtDNA. This effect was significantly lower in cells with disrupted mitochondria fission or repression of the autophagy-related genes ATG8, ATG32 or ATG33, implying that heteroplasmic zygotes activate mitochondrial degradation in response to the depolarization. Moreover, the rate of mitochondrially targeted GFP turnover was higher in zygotes treated with uncoupler than in haploid cells or untreated zygotes. Finally, we showed that vacuoles of zygotes with uncoupler-activated autophagy contained DNA. Taken together, our data demonstrate that mitochondrial depolarization inhibits clonal expansion of selfish mtDNA and this effect depends on mitochondrial fission and autophagy. These observations suggest an activation of mitochondria quality control mechanisms in heteroplasmic yeast zygotes.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial depolarization in yeast zygotes inhibits clonal expansion of selfish mtDNA

Karavaeva

Golyshev

Смирнова

et al. 2017

Journal of Cell Science

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“…Yet another study, aimed at exploring the role of Isc1 in yeast, found that isc1Δ cells exhibited mitochondrial dysfunction, increased mitophagy, decreased stress tolerance, and decreased CLS. 85 Isc1 is an inositol phosphosphingolipid phospholipase that hydrolyzes sphingolipids to produce the waxy lipid molecule ceramide. The authors found that Isc1-mediated ceramide production directly affected mitochondrial dynamics, with obvious consequences for cellular life span.…”

Section: Lipid Homeostasis Autophagy and Clsmentioning

confidence: 99%

The role of autophagy in the regulation of yeast life span

Tyler

Johnson

2018

Annals of the New York Academy of Sciences

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The goal of the aging field is to develop novel therapeutic interventions that extend human health span and reduce the burden of age-related disease. While organismal aging is a complex, multifactorial process, a popular theory is that cellular aging is a significant contributor to the progressive decline inherent to all multicellular organisms. To explore the molecular determinants that drive cellular aging, as well as how to retard them, researchers have utilized the highly genetically tractable budding yeast Saccharomyces cerevisiae. Indeed, every intervention known to extend both cellular and organismal health span was identified in yeast, underlining the power of this approach. Importantly, a growing body of work has implicated the process of autophagy as playing a critical role in the delay of aging. This review summarizes recent reports that have identified a role for autophagy, or autophagy factors in the extension of yeast life span. These studies demonstrate (1) that yeast remains an invaluable tool for the identification and characterization of conserved mechanisms that promote cellular longevity and are likely to be relevant to humans, and (2) that the process of autophagy has been implicated in nearly all known longevity-promoting manipulations and thus represents an ideal target for interventions aimed at improving human health span.

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“…Are yeast cells able to get rid of mitochondria with low transmembrane potential? Although there are several works suggesting the role of mitophagy in yeast mitochondrial quality control 373839, a specific mitochondrial autophagy in yeast is normally induced by starvation 4041. The latter fact points at the role of mitophagy in maintaining energy and nitrogen balances.…”

Section: Aberrant Accumulation Of Mitochondrial Precursors In the Cytmentioning

confidence: 99%

How do yeast sense mitochondrial dysfunction?

et al. 2016

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Apart from energy transformation, mitochondria play important signaling roles. In yeast, mitochondrial signaling relies on several molecular cascades. However, it is not clear how a cell detects a particular mitochondrial malfunction. The problem is that there are many possible manifestations of mitochondrial dysfunction. For example, exposure to the specific antibiotics can either decrease (inhibitors of respiratory chain) or increase (inhibitors of ATP-synthase) mitochondrial transmembrane potential. Moreover, even in the absence of the dysfunctions, a cell needs feedback from mitochondria to coordinate mitochondrial biogenesis and/or removal by mitophagy during the division cycle. To cope with the complexity, only a limited set of compounds is monitored by yeast cells to estimate mitochondrial functionality. The known examples of such compounds are ATP, reactive oxygen species, intermediates of amino acids synthesis, short peptides, Fe-S clusters and heme, and also the precursor proteins which fail to be imported by mitochondria. On one hand, the levels of these molecules depend not only on mitochondria. On the other hand, these substances are recognized by the cytosolic sensors which transmit the signals to the nucleus leading to general, as opposed to mitochondria-specific, transcriptional response. Therefore, we argue that both ways of mitochondria-to-nucleus communication in yeast are mostly (if not completely) unspecific, are mediated by the cytosolic signaling machinery and strongly depend on cellular metabolic state.

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Ceramide signalling impinges on Sit4p and Hog1p to promote mitochondrial fission and mitophagy in Isc1p-deficient cells

Cited by 27 publications

References 46 publications

Mitochondrial depolarization in yeast zygotes inhibits clonal expansion of selfish mtDNA

Mitochondrial depolarization in yeast zygotes inhibits clonal expansion of selfish mtDNA

The role of autophagy in the regulation of yeast life span

How do yeast sense mitochondrial dysfunction?

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