Regulation of Cell Death Induced by Acetic Acid in Yeasts

Abstract

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.

Saccharomyces cerevisiae Cells Lacking the Zinc Vacuolar Transporter Zrt3 Display Improved Ethanol Productivity in Lignocellulosic Hydrolysates

“…This hypothesis is in agreement with the observation that cells pre-adapted to acid stress, where the activity of catalases is enhanced, are resistant to AA-RCD [27]. Although other studies obtained by these authors, as well as by others, are not conclusive about the effect of RCD-inducing concentrations of AA on catalase or superoxide dismutase (SOD) activities, there is a consensus that increased activity of catalases protects cells from AA-RCD [24]. Thus, the results obtained in the current study suggest that the higher activity of catalases endows the zrt3∆ mutant with greater resistance to AA, in accordance with a major role of hydrogen peroxide detoxification in the prevention of AA-RCD [21].…”

“…Above a certain concentration threshold, it inhibits yeast cell growth by hindering metabolic functions through intracellular accumulation and acidification [18][19][20][21]. At high concentrations, it induces a mitochondrial-mediated regulated cell death (RCD) process with features similar to mammalian apoptosis [22,23], namely, reactive oxygen species (ROS) accumulation [23,24]. AA-induced RCD (AA-RCD) also involves a partial permeabilization of the vacuolar membrane and the release of the Pep4 protease to the cytosol while inhibiting autophagy [25].…”

A Systematic Survey of Characteristic Features of Yeast Cell Death Triggered by External Factors

“…With increasing exposure time, sodium selenite causes nuclear fragmentation and Aif1dependent apoptosis [170] 3.3.5. Acids Weak acids, namely acetic acid, have been thoroughly studied for their effect on yeast cell death and these studies have been extensively reviewed [171,172]. They are thought to act mostly via acidification of the internal environment of the cells, since under low pH in the external medium, weak acids are undissociated and thus can permeate the PM.…”

Cdk8 Kinase Module: A Mediator of Life and Death Decisions in Times of Stress

“…In yeast, many regulated cell death hallmarks are observed following stress treatment (e.g., H 2 O 2 or acetic acid) [ 207 , 208 , 209 ]. A critical difference from mammalian RCD pathways is that yeast lack orthologues of BAX and BAK.…”

“…Stress-induced mitochondrial hyper-fission is also associated with the release of these sequestered apoptotic factors and DNM1 deletion protects yeast cells from RCD [ 204 , 211 ]. As the release of pro-apoptotic factors from the mitochondria is a hallmark of RCD, it is generally accepted that yeast can execute RCD pathways following stress [ 209 ]. It also suggests an evolutionary linkage of these regulatory pathways [ 208 ].…”