Saccharomyces cerevisiae mitochondrial Por1/yVDAC1 (voltage-dependent anion channel 1) interacts physically with the MBOAT O-acyltransferase Gup1/HHATL in the control of cell wall integrity and programmed cell death

Abstract Background Programmed 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. Results In 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. Conclusions The 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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A Role for Voltage-Dependent Anion Channel Vdac1 in Polyglutamine-Mediated Neuronal Cell Death

PLoS ONE ◽

10.1371/journal.pone.0001170 ◽

2007 ◽

Vol 2 (11) ◽

pp. e1170 ◽

Cited By ~ 43

Author(s):

Tanay Ghosh ◽

Neeraj Pandey ◽

Arindam Maitra ◽

Samir K. Brahmachari ◽

Beena Pillai

Keyword(s):

Cell Death ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Anion Channel ◽

Voltage Dependent Anion Channel ◽

Voltage Dependent

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Cell fusion in yeast is negatively regulated by components of the cell wall integrity pathway

Molecular Biology of the Cell ◽

10.1091/mbc.e18-04-0236 ◽

2019 ◽

Vol 30 (4) ◽

pp. 441-452 ◽

Cited By ~ 2

Author(s):

Allison E. Hall ◽

Mark D. Rose

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Death ◽

Cell Wall ◽

Yeast Cell ◽

Cell Fusion ◽

Cell Walls ◽

Cell Wall Integrity ◽

Fusion Genes ◽

Cell Wall Degradation ◽

Cell Wall Integrity Pathway

During mating, Saccharomyces cerevisiae cells must degrade the intervening cell wall to allow fusion of the partners. Because improper timing or location of cell wall degradation would cause lysis, the initiation of cell fusion must be highly regulated. Here, we find that yeast cell fusion is negatively regulated by components of the cell wall integrity (CWI) pathway. Loss of the cell wall sensor, MID2, specifically causes “mating-induced death” after pheromone exposure. Mating-induced death is suppressed by mutations in cell fusion genes ( FUS1, FUS2, RVS161, CDC42), implying that mid2Δ cells die from premature fusion without a partner. Consistent with premature fusion, mid2Δ shmoos had thinner cell walls and lysed at the shmoo tip. Normally, Cdc42p colocalizes with Fus2p to form a focus only when mating cells are in contact (prezygotes) and colocalization is required for cell fusion. However, Cdc42p was aberrantly colocalized with Fus2p to form a focus in mid2Δ shmoos. A hyperactive allele of the CWI kinase Pkc1p ( PKC1*) caused decreased cell fusion and Cdc42p localization in prezygotes. In shmoos, PKC1* increased Cdc42p localization; however, it was not colocalized with Fus2p or associated with cell death. We conclude that Mid2p and Pkc1p negatively regulate cell fusion via Cdc42p and Fus2p.

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Mitochondrial Voltage-Dependent Anion Channel Protein Por1 Positively Regulates the Nuclear Localization of Saccharomyces cerevisiae AMP-Activated Protein Kinase

mSphere ◽

10.1128/msphere.00482-17 ◽

2018 ◽

Vol 3 (1) ◽

Author(s):

Aishwarya Shevade ◽

Vera Strogolova ◽

Marianna Orlova ◽

Chay Teng Yeo ◽

Sergei Kuchin

Keyword(s):

Saccharomyces Cerevisiae ◽

Nuclear Localization ◽

Atp Release ◽

Anion Channel ◽

Voltage Dependent Anion Channel ◽

Catalytic Activation ◽

Evolutionarily Conserved ◽

Voltage Dependent ◽

Energy Limitation ◽

Amp Activated Protein Kinase

AMP-activated protein kinases (AMPKs) sense energy limitation and regulate transcription and metabolism in eukaryotes from yeast to humans. In mammals, AMPK responds to increased AMP-to-ATP or ADP-to-ATP ratios and is implicated in diabetes, heart disease, and cancer. Mitochondria produce ATP and are generally thought to downregulate AMPK. Indeed, some antidiabetic drugs activate AMPK by affecting mitochondrial respiration. ATP release from mitochondria is mediated by evolutionarily conserved proteins known as voltage-dependent anion channels (VDACs). One would therefore expect VDACs to serve as negative regulators of AMPK. However, our experiments in yeast reveal the existence of an opposite relationship. We previously showed that Saccharomyces cerevisiae VDACs Por1 and Por2 positively regulate AMPK/Snf1 catalytic activation. Here, we show that Por1 also plays an important role in promoting AMPK/Snf1 nuclear localization. Our counterintuitive findings could inform research in areas ranging from diabetes to cancer to fungal pathogenesis.

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MAVS Regulates Apoptotic Cell Death by Decreasing K48-Linked Ubiquitination of Voltage-Dependent Anion Channel 1

Molecular and Cellular Biology ◽

10.1128/mcb.00030-13 ◽

2013 ◽

Vol 33 (16) ◽

pp. 3137-3149 ◽

Cited By ~ 39

Author(s):

Kai Guan ◽

Zirui Zheng ◽

Ting Song ◽

Xiang He ◽

Changzhi Xu ◽

...

Keyword(s):

Cell Death ◽

Apoptotic Cell ◽

Anion Channel ◽

Apoptotic Cell Death ◽

Type I ◽

Voltage Dependent Anion Channel ◽

Voltage Dependent ◽

Consequent Reduction ◽

Mitochondrial Antiviral Signaling ◽

Induced Apoptosis

The mitochondrial antiviral signaling protein MAVS (IPS-1, VISA, or Cardif) plays an important role in the host defense against viral infection by inducing type I interferon. Recent reports have shown that MAVS is also critical for virus-induced apoptosis. However, the mechanism of MAVS-mediated apoptosis induction remains unclear. Here, we show that MAVS binds to voltage-dependent anion channel 1 (VDAC1) and induces apoptosis by caspase-3 activation, which is independent of its role in innate immunity. MAVS modulates VDAC1 protein stability by decreasing its degradative K48-linked ubiquitination. In addition, MAVS knockout mouse embryonic fibroblasts (MEFs) display reduced VDAC1 expression with a consequent reduction of the vesicular stomatitis virus (VSV)-induced apoptosis response. Notably, the upregulation of VDAC1 triggered by VSV infection is completely abolished in MAVS knockout MEFs. We thus identify VDAC1 as a target of MAVS and describe a novel mechanism of MAVS control of virus-induced apoptotic cell death.

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In self-defence: hexokinase promotes voltage-dependent anion channel closure and prevents mitochondria-mediated apoptotic cell death

Biochemical Journal ◽

10.1042/bj20031465 ◽

2004 ◽

Vol 377 (2) ◽

pp. 347-355 ◽

Cited By ~ 259

Author(s):

Heftsi AZOULAY-ZOHAR ◽

Adrian ISRAELSON ◽

Salah ABU-HAMAD ◽

Varda SHOSHAN-BARMATZ

Keyword(s):

Cell Death ◽

Cell Survival ◽

Molecular Mechanisms ◽

Apoptotic Cell ◽

Direct Interaction ◽

Anion Channel ◽

Mitochondrial Outer Membrane ◽

Voltage Dependent Anion Channel ◽

Metabolic Intermediate ◽

Voltage Dependent

In tumour cells, elevated levels of mitochondria-bound isoforms of hexokinase (HK-I and HK-II) result in the evasion of apoptosis, thereby allowing the cells to continue proliferating. The molecular mechanisms by which bound HK promotes cell survival are not yet fully understood. Our studies relying on the purified mitochondrial outer membrane protein VDAC (voltage-dependent anion channel), isolated mitochondria or cells in culture suggested that the anti-apoptotic activity of HK-I occurs via modulation of the mitochondrial phase of apoptosis. In the present paper, a direct interaction of HK-I with bilayer-reconstituted purified VDAC, inducing channel closure, is demonstrated for the first time. Moreover, HK-I prevented the Ca2+-dependent opening of the mitochondrial PTP (permeability transition pore) and release of the pro-apoptotic protein cytochrome c. The effects of HK-I on VDAC activity and PTP opening were prevented by the HK reaction product glucose 6-phosphate, a metabolic intermediate in most biosynthetic pathways. Furthermore, glucose 6-phosphate re-opened both the VDAC and the PTP closed by HK-I. The HK-I-mediated effects on VDAC and PTP were not observed using either yeast HK or HK-I lacking the N-terminal hydrophobic peptide responsible for binding to mitochondria, or in the presence of an antibody specific for the N-terminus of HK-I. Finally, HK-I overexpression in leukaemia-derived U-937 or vascular smooth muscle cells protected against staurosporine-induced apoptosis, with a decrease of up to 70% in cell death. These results offer insight into the mechanisms by which bound HK promotes tumour cell survival, and suggests that its overexpression not only ensures supplies of energy and phosphometabolites, but also reflects an anti-apoptotic defence mechanism.

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Functions of BCL-XLat the Interface between Cell Death and Metabolism

International Journal of Cell Biology ◽

10.1155/2013/705294 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 51

Author(s):

Judith Michels ◽

Oliver Kepp ◽

Laura Senovilla ◽

Delphine Lissa ◽

Maria Castedo ◽

...

Keyword(s):

Cell Death ◽

Mitochondrial Permeability Transition ◽

Atp Synthesis ◽

Anion Channel ◽

Permeability Transition ◽

Short Review ◽

Mitochondrial Outer Membrane ◽

Voltage Dependent Anion Channel ◽

Regulated Necrosis ◽

Voltage Dependent

The BCL-2 homolog BCL-XL, one of the two protein products ofBCL2L1, has originally been characterized for its prominent prosurvival functions. Similar to BCL-2, BCL-XLbinds to its multidomain proapoptotic counterparts BAX and BAK, hence preventing the formation of lethal pores in the mitochondrial outer membrane, as well as to multiple BH3-only proteins, thus interrupting apical proapoptotic signals. In addition, BCL-XLhas been suggested to exert cytoprotective functions by sequestering a cytosolic pool of the pro-apoptotic transcription factor p53 and by binding to the voltage-dependent anion channel 1 (VDAC1), thereby inhibiting the so-called mitochondrial permeability transition (MPT). Thus, BCL-XLappears to play a prominent role in the regulation of multiple distinct types of cell death, including apoptosis and regulated necrosis. More recently, great attention has been given to the cell death-unrelated functions of BCL-2-like proteins. In particular, BCL-XLhas been shown to modulate a number of pathophysiological processes, including—but not limited to—mitochondrial ATP synthesis, protein acetylation, autophagy and mitosis. In this short review article, we will discuss the functions of BCL-XLat the interface between cell death and metabolism.

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