Contacts in Death: The Role of the ER–Mitochondria Axis in Acetic Acid-Induced Apoptosis in Yeast

Martins, Vítor Manuel Tavares; Fernandes, Tania; Lopes, Diana; Afonso, Catarina; Domingues, Rosário M.; Côrte‐Real, Manuela; Sousa, Maria João

doi:10.1016/j.jmb.2018.11.002

Cited by 14 publications

(13 citation statements)

References 106 publications

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“…Acetic acid-induced mitochondrial degradation was demonstrated by several authors ( Fannjiang et al, 2004 ; Pereira et al, 2010 ; Rego et al, 2012 ; Pereira et al, 2013 ; Dong et al, 2017 ; Martins et al, 2019 ) and it was shown that the normal tubular mitochondrial network becomes fragmented and deformed, acquiring a punctate pattern ( Fannjiang et al, 2004 ; Pereira et al, 2010 ; Rego et al, 2012 , 2018 ; Longo et al, 2015 ; Trindade et al, 2016 ), or even forming clusters in some mutant cells ( Pereira et al, 2010 ; Rego et al, 2012 ) in an actin-dependent process ( Pereira et al, 2010 ). Mitochondrial outer membrane permeabilization (MOMP) associated with cytochrome c release, a central event in mammalian intrinsic apoptosis, was also characterized: this hallmark in AA-RCD has been studied by assessing permeabilization of the outer mitochondrial membrane and maintenance of IMM integrity by in vitro enzymatic assays ( Pereira et al, 2007 ; Rego et al, 2012 , 2014a ), and cytochrome c release by western blot and/or spectra analysis ( Ludovico et al, 2002 ; Pereira et al, 2007 ; Giannattasio et al, 2008 ; Guaragnella et al, 2010a , b , 2011 , 2013 ; Rego et al, 2014a , 2018 , 2020 ; Guerreiro et al, 2016 ; Trindade et al, 2016 ; Martins et al, 2019 ). Besides mitochondria, a functional vacuole also seems to be crucial in AA-RCD ( Schauer et al, 2009 ), involving vacuolar membrane permeabilization and subsequent release of Pep4p, the yeast ortholog of mammalian cathepsin D (CatD), which acts on mitochondrial degradation ( Pereira et al, 2010 ).…”

Section: Hallmarks Of Acetic Acid-induced Regulated Cell Deathmentioning

confidence: 99%

“…It has also been reported that acetic acid perturbs sphingolipid balance, which in turn regulates AA-RCD, by altering the mitochondrial levels of specific sphingolipid species, namely by decreasing most phosphorylated dihydro- and phytosphingosines and increasing the levels of dihydroceramide ( Rego et al, 2012 , 2018 ). Finally, acetic acid was also shown to impact mitochondrial phospholipids, inducing a reduction of almost 50% in their relative phosphatidylinositol content ( Martins et al, 2019 ).…”

Section: Hallmarks Of Acetic Acid-induced Regulated Cell Deathmentioning

confidence: 99%

“…A subsequent study showed that the Endoplasmic Reticulum-Mitochondria Encounter Structure (ERMES), a physical point of crosstalk between the ER and mitochondria, is involved in AA-RCD ( Martins et al, 2019 ). Though ERMES is thought to participate in lipid exchange and calcium signaling, its role is not yet fully understood ( Michel and Kornmann, 2012 ).…”

Section: Genetic Modulation Of Acetic Acid-induced Regulated Cell Deathmentioning

confidence: 99%

“…This complex is formed by the ER-anchored protein Mmm1p, cytosolic Mdm12p and two outer mitochondrial membrane proteins, Mdm10p and Mdm34p. Martins et al (2019) showed that mdm10 Δ, mdm12 Δ, and mdm34 Δ cells display a resistant phenotype upon acetic acid challenge, exhibiting a significant delay in the appearance of several apoptotic markers such as loss of mitochondrial transmembrane potential, mitochondrial degradation and ROS accumulation, as well as in the loss of plasma membrane integrity evidencing secondary necrosis. Additionally, cells lacking either Mdm10p or Mdm34p were unable to release cytochrome c from mitochondria, while mdm12 Δ cells lost the majority of their mitochondrial cytochrome c pool.…”

Section: Genetic Modulation Of Acetic Acid-induced Regulated Cell Deathmentioning

confidence: 99%

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Regulation of Cell Death Induced by Acetic Acid in Yeasts

Chaves

Rego

Martins

et al. 2021

Front. Cell Dev. Biol.

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Acetic acid has long been considered a molecule of great interest in the yeast research field. It is mostly recognized as a by-product of alcoholic fermentation or as a product of the metabolism of acetic and lactic acid bacteria, as well as of lignocellulosic biomass pretreatment. High acetic acid levels are commonly associated with arrested fermentations or with utilization as vinegar in the food industry. Due to its obvious interest to industrial processes, research on the mechanisms underlying the impact of acetic acid in yeast cells has been increasing. In the past twenty years, a plethora of studies have addressed the intricate cascade of molecular events involved in cell death induced by acetic acid, which is now considered a model in the yeast regulated cell death field. As such, understanding how acetic acid modulates cellular functions brought about important knowledge on modulable targets not only in biotechnology but also in biomedicine. Here, we performed a comprehensive literature review to compile information from published studies performed with lethal concentrations of acetic acid, which shed light on regulated cell death mechanisms. We present an historical retrospective of research on this topic, first providing an overview of the cell death process induced by acetic acid, including functional and structural alterations, followed by an in-depth description of its pharmacological and genetic regulation. As the mechanistic understanding of regulated cell death is crucial both to design improved biomedical strategies and to develop more robust and resilient yeast strains for industrial applications, acetic acid-induced cell death remains a fruitful and open field of study.

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Section: Hallmarks Of Acetic Acid-induced Regulated Cell Deathmentioning

confidence: 99%

Section: Hallmarks Of Acetic Acid-induced Regulated Cell Deathmentioning

confidence: 99%

Section: Genetic Modulation Of Acetic Acid-induced Regulated Cell Deathmentioning

confidence: 99%

Section: Genetic Modulation Of Acetic Acid-induced Regulated Cell Deathmentioning

confidence: 99%

See 2 more Smart Citations

Regulation of Cell Death Induced by Acetic Acid in Yeasts

Chaves

Rego

Martins

et al. 2021

Front. Cell Dev. Biol.

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“…In turn, Ac induced the degradation of Atg22p. Reactive oxygen species (ROS) accumulation and mitochondria degradation were also involved in Ac-induced apoptosis [17, 22]. ROS production during cell metabolism by mitochondrial electron transport chain or non-mitochondrial pathway is beneficial to signal transmission [23].…”

Section: Discussionmentioning

confidence: 99%

Deletion of Atg22 gene contributes to reduce programmed cell death induced by acetic acid stress in Saccharomyces cerevisiae

Dong

Wang

et al. 2019

Biotechnol Biofuels

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BackgroundProgrammed cell death (PCD) induced by acetic acid, the main by-product released during cellulosic hydrolysis, cast a cloud over lignocellulosic biofuel fermented by Saccharomyces cerevisiae and became a burning problem. Atg22p, an ignored integral membrane protein located in vacuole belongs to autophagy-related genes family; prior study recently reported that it is required for autophagic degradation and efflux of amino acids from vacuole to cytoplasm. It may alleviate the intracellular starvation of nutrition caused by Ac and increase cell tolerance. Therefore, we investigate the role of atg22 in cell death process induced by Ac in which attempt is made to discover new perspectives for better understanding of the mechanisms behind tolerance and more robust industrial strain construction.ResultsIn this study, we compared cell growth, physiological changes in the absence and presence of Atg22p under Ac exposure conditions. It is observed that disruption and overexpression of Atg22p delays and enhances acetic acid-induced PCD, respectively. The deletion of Atg22p in S. cerevisiae maintains cell wall integrity, and protects cytomembrane integrity, fluidity and permeability upon Ac stress by changing cytomembrane phospholipids, sterols and fatty acids. More interestingly, atg22 deletion increases intracellular amino acids to aid yeast cells for tackling amino acid starvation and intracellular acidification. Further, atg22 deletion upregulates series of stress response genes expression such as heat shock protein family, cell wall integrity and autophagy.ConclusionsThe findings show that Atg22p possessed the new function related to cell resistance to Ac. This may help us have a deeper understanding of PCD induced by Ac and provide a new strategy to improve Ac resistance in designing industrial yeast strains for bioethanol production during lignocellulosic biofuel fermentation.

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Mitochondria-associated membranes in the maintenance of cell homeostasis

Camougrand

Manon

2021

Mitochondrial Physiology and Vegetal Molecules

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Contacts in Death: The Role of the ER–Mitochondria Axis in Acetic Acid-Induced Apoptosis in Yeast

Cited by 14 publications

References 106 publications

Regulation of Cell Death Induced by Acetic Acid in Yeasts

Regulation of Cell Death Induced by Acetic Acid in Yeasts

Deletion of Atg22 gene contributes to reduce programmed cell death induced by acetic acid stress in Saccharomyces cerevisiae

Mitochondria-associated membranes in the maintenance of cell homeostasis

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