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Articles by G. Kroemer
Total Records ( 2 ) for G. Kroemer
  F Madeo , T Eisenberg and G. Kroemer

Cellular defense mechanisms, including the unfolded protein response (UPR) and autophagy, attempt to resolve toxic protein aggregates, which are common denominators of neurodegenerative diseases. In this issue of Genes & Development, Hetz and colleagues (pp. 2294–2306) surprisingly show that inhibition of the UPR by knockout of XBP-1 causes a massive increase in autophagy, enhances clearance of superoxide dismutase 1 (SOD1) aggregates, and delays the development of amyotrophic lateral sclerosis. These findings suggest the existence of a homeostatic—if not hormetic—balance between distinct cellular defense mechanisms.

  J Yuan and G. Kroemer

A canonical regulatory pathway involving the members of the Bcl-2 and caspase families has been established to regulate developmental apoptosis in nematodes and flies. However, mutant mice that have major deficiencies in this apoptosis pathway show only relatively minor developmental defects. Recent revelations indicate that multiple mechanisms are involved in regulating cell death during mammalian development, tissue homeostasis, and pathological cell loss. Here, we critically evaluate the evidence demonstrating the existence of alternative cell death mechanisms, including apoptosis of lower organisms in the absence of canonical apoptosis mediators, autophagic cell death, necroptosis, elimination by shedding, keratinocyte death by cornification, and cell–cell cannibalism by entosis. The physiological relevance of alternative cell death mechanisms as primary and backup mechanisms is discussed.

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