Another face of cell death

For multicellular organisms, cell death can be as important as life itself. Programmed cell death (PCD) plays key roles during embryonic development by eliminating superfluous cells. in adult organisms, the homeostasis of tissues partly depends on eliminating damaged cells by PCD; otherwise, severe consequences can ensue. For instance, failure to eliminate damaged cells may lead to cancer. The term programmed in PCD implies the orderly intervention of gene products in the execution of cell death following an intrinsic or an extrinsic signal. PCD also infers regulated forms of death as opposed to accidental. As such, it is possible to alter the net outcome of PCD by genetically modifying the levels/activ-ities of the intervening gene products. initially, PCD was classified into 3 major types: apoptosis, autophagic cell death, and programmed necrosis. 1 This classification was based mostly on morphological differences between cells committed to these different forms of PCD. More recently, the inclusion of biochemical markers in the classifications of PCD has portrayed a more complex picture, composed of different facets of cell death, each involving diverse modules of the 3 main suicide pathways. 2 interestingly, in this issue of Cell Cycle, sheibani et al. 3 report a new form of PCD that they call " liponecrosis. " in previous work, the authors have assessed the effect of palmitoleic acid (POA) on the viability of Saccharomyces cerevisiae, and have demonstrated that a short exposure (2 h) to this fatty acid severely reduces clonogenicity. 4,5 in the current work, the authors investigate the death mechanism induced by exposure to POA. Previously, they observed that a pex5Δ mutation, which impairs peroxisomal fatty acid oxidation, enhanced the POA-death phenotype. This observation suggested that healthy mitochondria might be required to protect cells from this type of death, leading to the hypothesis that macromitophagy could be involved in the defense against POA-induced lethality. To test this hypothesis, the authors examined the ATG32 gene that is specifically involved in macromitophagy. 6,7 The results were conclusive; an atg32Δ strain is more sensitive to death triggered by POA. interestingly, the reduction of cell viability by the POA mechanism appears to progress with the chronological age of a yeast cell, indicating that it is an age-related modality of cell death. Atg1p is a serine/threonine kinase protein kinase that orchestrates macroautoph-agy; the en masse degradation of components and organelles of the cell. 8 Macroautophagy has a pro-survival function against apoptotic death, …