Doctor Jekyll and Mister Hyde: autophagy can promote both cell survival and cell death

Eskelinen, Eeva‐Liisa

doi:10.1038/sj.cdd.4401721

Cited by 76 publications

(65 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It would seem that prolonged starvation would, in fact, lead cells to consume themselves to death or initiate apoptosis. In fact, under certain conditions, autophagy can kill cells through a process known as autophagic cell death or cell death type II (for review, see Eskelinen 2005). However, feedback mechanisms may exist to prevent cell death caused by prolonged activation of autophagy, and one appears to require mTORC1-dependent phosphorylation of DAP1 (death-associated protein 1) (Koren et al 2010).…”

Section: Mtorc1 Directly Regulates Autophagymentioning

confidence: 99%

mTOR-Dependent Cell Survival Mechanisms

Hung

García-Haro

Sparks

et al. 2012

Cold Spring Harbor Perspectives in Biology

163

135

View full text Add to dashboard Cite

The mechanistic target of rapamycin (mTOR) kinase is a conserved regulator of cell growth, proliferation, and survival. In cells, mTOR is the catalytic subunit of two complexes called mTORC1 and mTORC2, which have distinct upstream regulatory signals and downstream substrates. mTORC1 directly senses cellular nutrient availability while indirectly sensing circulating nutrients through growth factor signaling pathways. Cellular stresses that restrict growth also impinge on mTORC1 activity. mTORC2 is less well understood and appears only to sense growth factors. As an integrator of diverse growth regulatory signals, mTOR evolved to be a central signaling hub for controlling cellular metabolism and energy homoeostasis, and defects in mTOR signaling are important in the pathologies of cancer, diabetes, and aging. Here we discuss mechanisms by which each mTOR complex might regulate cell survival in response to metabolic and other stresses.

show abstract

Section: Mtorc1 Directly Regulates Autophagymentioning

confidence: 99%

mTOR-Dependent Cell Survival Mechanisms

Hung

García-Haro

Sparks

et al. 2012

Cold Spring Harbor Perspectives in Biology

163

135

View full text Add to dashboard Cite

show abstract

“…RAK: In several reviews published in this issue of Cell Death Differentiation, several manuscripts describe autophagy in detail, [2][3][4][5][6][7][8][9][10] while Lippens et al 11 contrast two distinct forms of death, apoptosis and cornification in the skin, see also for review. 12 Although these two processes may appear to have superficial similarities, their detailed mechanisms are largely different.…”

mentioning

confidence: 99%

How many ways to die? How many different models of cell death?

2005

View full text Add to dashboard Cite

A very late summer afternoon, becoming dark, after a very long days work in an obscure field in the English Midlands near a brewery. Three rats (all, of course, from the well known upper class Sprague-Dawley family) are drinking a well-earned beer, y. one is strongly inhaling a fag, another playing with his nuts, the last just trying to pile up papers for the next issue of the Midland rat's chronicley

show abstract

“…One way to test this would be to examine cell death in Apaf-1 mutants that also lack key autophagy genes. Although there has been a debate over whether autophagy is a nonapoptotic form of PCD or a prosurvival mechanism (Lockshin and Zakeri, 2004;Eskelinen, 2005;Levine and Yuan, 2005), there is a growing consensus that, depending on the circumstances, it can serve both roles (Uchiyama, 2001;Yue et al, 2002;Shimizu et al, 2004;Komatsu et al, 2006;Nixon, 2006;Berry and Baehrecke, 2007;Calderó et al, 2007;Fimia et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Developing Postmitotic Mammalian NeuronsIn VivoLacking Apaf-1 Undergo Programmed Cell Death by a Caspase-Independent, Nonapoptotic Pathway Involving Autophagy

Oppenheim¹,

Blomgren²,

Ethell³

et al. 2008

J. Neurosci.

View full text Add to dashboard Cite

Previous studies have shown that caspases and Apaf-1 are required for the normal programmed cell death (PCD) in vivo of immature postmitotic neurons and mitotically active neuronal precursor cells. In contrast, caspase activity is not necessary for the normal PCD of more mature postmitotic neurons that are establishing synaptic connections. Although normally these cells use caspases for PCD, in the absence of caspase activity these neurons undergo a distinct nonapoptotic type of degeneration. We examined the survival of these more mature postmitotic neuronal populations in mice in which Apaf-1 has been genetically deleted and find that they exhibit quantitatively normal PCD of developing postmitotic neurons. We next characterized the morphological mode of PCD in these mice and show that the neurons degenerate by a caspase-independent, nonapoptotic pathway that involves autophagy. However, autophagy does not appear to be involved in the normal PCD of postmitotic neurons in which caspases and Apaf-1 are present and functional because quantitatively normal neuronal PCD occurred in the absence of a key gene required for autophagy (ATG7). Finally, we examined the possible role of another caspase-independent type of neuronal PCD involving the apoptosis-inducing factor (AIF). Mice deficient in AIF also exhibit quantitatively normal PCD of postmitotic neurons after caspase inhibition. Together, these data indicate that, when key components of the type 1 apoptotic pathway (i.e., caspases and Apaf-1) are perturbed in vivo, developing postmitotic neurons nonetheless undergo quantitatively normal PCD by a caspase-independent pathway involving autophagy and not requiring AIF.

show abstract

Doctor Jekyll and Mister Hyde: autophagy can promote both cell survival and cell death

Cited by 76 publications

References 22 publications

mTOR-Dependent Cell Survival Mechanisms

mTOR-Dependent Cell Survival Mechanisms

How many ways to die? How many different models of cell death?

Developing Postmitotic Mammalian NeuronsIn VivoLacking Apaf-1 Undergo Programmed Cell Death by a Caspase-Independent, Nonapoptotic Pathway Involving Autophagy

Contact Info

Product

Resources

About