Series |

Cell death and autophagy

Homeostatic and pathological cell death can take diverse forms that, when disrupted, can lead to diseases such as cancer and degenerative conditions. For a long time, cell death was thought to occur through apoptosis, which is a programmed event that often confers an advantage to the organism, or through necrosis induced by external factors such as trauma or infection. However, it is now clear that the biological reality is more complex. Various forms of programmed necrosis exist, including necroptosis, and cell death can also occur as a result of autophagy – a process that usually breaks down cellular components to aid cell survival during starvation. This article series highlights the progress that has been made in our understanding of different modes of cell death and autophagy and how they function as both a cell survival and cell death mechanism. Together, these articles highlight the defining features of each pathway, as well as the interplay between different cell death modalities in particular biological contexts.

Reviews

  • Nature Reviews Molecular Cell Biology | Review Article

    Recent studies in model organisms uncovered prominent links between autophagy and ageing, suggesting that by removing superfluous or damaged cellular content through lysosomal degradation, autophagy supports tissue and organismal fitness and promotes longevity. Thus, autophagy induction could be considered a strategy to extend lifespan.

    • Malene Hansen
    • , David C. Rubinsztein
    •  &  David W. Walker
  • Nature Reviews Molecular Cell Biology | Review Article

    The selective degradation of cellular components via chaperone-mediated autophagy (CMA) functions to regulate a wide range of cellular processes, from metabolism to DNA repair and cellular reprogramming. Recent in vivo studies have enabled to dissect key roles of CMA in ageing and ageing-associated disorders such as cancer and neurodegeneration.

    • Susmita Kaushik
    •  &  Ana Maria Cuervo
  • Nature Reviews Molecular Cell Biology | Review Article

    Autophagy is a process of cellular self-consumption that promotes cell survival in response to stress. Various human pathologies, including cancer, neurodegeneration and inflammation, have been associated with aberrant autophagy, and recent studies of the mechanisms and regulation of autophagy in higher eukaryotes have suggested new therapeutic possibilities.

    • Ivan Dikic
    •  &  Zvulun Elazar
  • Nature Reviews Molecular Cell Biology | Review Article

    Recent studies that combine cell biology, structural and proteomic approaches have unravelled how ubiquitin is conjugated to damaged mitochondria through the PINK1–parkin pathway to promote mitophagy. The findings have revealed links between PINK1–parkin, antigen presentation and neuronal survival and have implications for the understanding of neurological disorders.

    • J. Wade Harper
    • , Alban Ordureau
    •  &  Jin-Mi Heo
  • Nature Reviews Molecular Cell Biology | Timeline

    Several years after the characterization of the role of receptor-interacting serine/threonine protein kinase 1 (RIPK1) in cell survival, inflammation and disease, RIPK1 was implicated in the regulation of a newly identified type of cell death known as necroptosis. This Timeline article describes the discoveries that shed light on the roles of RIPK1, RIPK3, mixed-lineage kinase domain-like protein (MLKL) and other regulators of necroptosis in controlling cell fate.

    • Ricardo Weinlich
    • , Andrew Oberst
    • , Helen M. Beere
    •  &  Douglas R. Green
  • Nature Reviews Molecular Cell Biology | Review Article

    Selective autophagy pathways engage selective autophagy receptors (SARs) that identify and bind to cellular cargoes (proteins or organelles) destined for degradation. Recent yeast studies have provided insights into the regulation and mechanisms underlying SAR function. As these mechanisms are conserved from yeast to mammals, it is now possible to formulate general principles of how selectivity during autophagy is achieved.

    • Jean-Claude Farré
    •  &  Suresh Subramani