Iron is an essential micronutrient that is problematic for biological systems since it is toxic as it generates free radicals by interconverting between ferrous (Fe) and ferric (Fe) forms. Additionally, even though iron is abundant, it is largely insoluble so cells must treat biologically available iron as a valuable commodity. Thus elaborate mechanisms have evolved to absorb, re-cycle and store iron while minimizing toxicity. Focusing on rarely encountered situations, most of the existing literature suggests that iron toxicity is common. A more nuanced examination clearly demonstrates that existing regulatory processes are more than adequate to limit the toxicity of iron even in response to iron overload. Only under pathological or artificially harsh situations of exposure to excess iron does it become problematic. Here we review iron metabolism and its toxicity as well as the literature demonstrating that intracellular iron is not toxic but a stress responsive programmed cell death-inducing second messenger.
Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the authors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the progress of this vibrant field of research.
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