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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Electroactive materials allow the modulation of cell–materials interactions and cell fate, leading to advanced tissue regeneration strategies. Nevertheless, their effect at the cellular level is still poorly understood. In this context, the proteome analysis of C2C12 cell differentiation cultured on piezoelectric polymer films with null average surface charge (non-poled), net positive surface charge (poled +), and net negative surface charge (poled −) has been addressed. Protein/pathway alterations for skeletal muscle development were identified comparing proteomic profiles of C2C12 cells differentiated on poly­(vinylidene fluoride), with similar cells differentiated on a polystyrene plate (control), using label-free liquid chromatography–tandem mass spectrometry (LC–MS/MS). Only significantly expressed proteins (P < 0.01, analysis of variance) were used for bioinformatic analyses. A total of 37 significantly expressed proteins were detected on the C2C12 proteome with PVDF “poled −” at 24 h, whereas on the PVDF “poled +”, a total of 105 significantly expressed proteins were considered. At 5 days of differentiation, the number of significantly expressed proteins decreased to 23 and 31 in cells grown on negative and positive surface charge, respectively, the influence of surface charge being more explicit in some proteins. In both cases, proteins such as Fbn1, Hspg2, Rcn3, Tgm2, Mylpf, Anxa2, and Anxa6, involved in calcium-related signaling, were highly expressed during myoblast differentiation. Furthermore, some proteins involved in muscle contraction (Acta2, Anxa2, and Anxa6) were detected in the PVDF “poled +” sample. Upregulation of several proteins that enhance skeletal muscle development was detected in the PVDF “poled −” sample, including Ckm (422%), Tmem14c (384%), Serpinb6a (460%), adh7 (199%), and Car3 (171%), while for the “poled +” samples, these proteins were also upregulated at a smaller magnitude (254, 317, 253, 123, and 72%, respectively). Other differentially expressed proteins such as Mylpf (189%), Mybph (168%), and Mbnl1 (168%) were upregulated only in PVDF “poled −” samples, while Hba-a1 levels (581%) were increased in the PVDF “poled +” sample. On the other hand, cells cultured on non-poled samples have no differences with respect to the ones cultured on the control, in contrary to the poled films, with overall surface charge, demonstrating the relevance of scaffold surface charge on cell behavior. This study demonstrates that both positive and negative overall surface charges promote the differentiation of C2C12 cells through involvement of proteins related with the contraction of the skeletal muscle cells, with a more pronounced effect with the negative charged surfaces.

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