Sphingolipids: Regulators of crosstalk between apoptosis and autophagy

Research output: Contribution to journalReview article

162 Citations (Scopus)

Abstract

Apoptosis and autophagy are two evolutionarily conserved processes that maintain homeostasis during stress. Although the two pathways utilize fundamentally distinct machinery, apoptosis and autophagy are highly interconnected and share many key regulators. The crosstalk between apoptosis and autophagy is complex, as autophagy can function to promote cell survival or cell death under various cellular conditions. The molecular mechanisms of crosstalk are beginning to be elucidated and have critical implications for the treatment of various diseases, such as cancer. Sphingolipids are a class of bioactive lipids that mediate many key cellular processes, including apoptosis and autophagy. By targeting several of the shared regulators, sphingolipid metabolites differentially regulate the induction of apoptosis and autophagy. Importantly, individual sphingolipid species appear to "switch" autophagy toward cell survival (e.g., sphingosine-1-phosphate) or cell death (e.g., ceramide, gangliosides). This review assesses the current understanding of sphingolipid-induced apoptosis and autophagy to address how sphingolipids mediate the "switch" between the cell survival and cell death. As sphingolipid metabolism is frequently dysregulated in cancer, sphingolipid-modulating agents, or sphingomimetics, have emerged as a novel chemotherapeutic strategy. Ultimately, a greater understanding of sphingolipid-mediated crosstalk between apoptosis and autophagy may be critical for enhancing the chemotherapeutic efficacy of these agents.

Original languageEnglish (US)
Pages (from-to)5-19
Number of pages15
JournalJournal of Lipid Research
Volume54
Issue number1
DOIs
StatePublished - Jan 1 2013

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Sphingolipids
Autophagy
Crosstalk
Apoptosis
Cell death
Cell Survival
Cells
Cell Death
Switches
Gangliosides
Ceramides
Metabolites
Metabolism
Machinery
Neoplasms
Homeostasis
Lipids

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

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title = "Sphingolipids: Regulators of crosstalk between apoptosis and autophagy",
abstract = "Apoptosis and autophagy are two evolutionarily conserved processes that maintain homeostasis during stress. Although the two pathways utilize fundamentally distinct machinery, apoptosis and autophagy are highly interconnected and share many key regulators. The crosstalk between apoptosis and autophagy is complex, as autophagy can function to promote cell survival or cell death under various cellular conditions. The molecular mechanisms of crosstalk are beginning to be elucidated and have critical implications for the treatment of various diseases, such as cancer. Sphingolipids are a class of bioactive lipids that mediate many key cellular processes, including apoptosis and autophagy. By targeting several of the shared regulators, sphingolipid metabolites differentially regulate the induction of apoptosis and autophagy. Importantly, individual sphingolipid species appear to {"}switch{"} autophagy toward cell survival (e.g., sphingosine-1-phosphate) or cell death (e.g., ceramide, gangliosides). This review assesses the current understanding of sphingolipid-induced apoptosis and autophagy to address how sphingolipids mediate the {"}switch{"} between the cell survival and cell death. As sphingolipid metabolism is frequently dysregulated in cancer, sphingolipid-modulating agents, or sphingomimetics, have emerged as a novel chemotherapeutic strategy. Ultimately, a greater understanding of sphingolipid-mediated crosstalk between apoptosis and autophagy may be critical for enhancing the chemotherapeutic efficacy of these agents.",
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Sphingolipids : Regulators of crosstalk between apoptosis and autophagy. / Young, Megan M.; Kester, Mark; Wang, Hong Gang.

In: Journal of Lipid Research, Vol. 54, No. 1, 01.01.2013, p. 5-19.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Sphingolipids

T2 - Regulators of crosstalk between apoptosis and autophagy

AU - Young, Megan M.

AU - Kester, Mark

AU - Wang, Hong Gang

PY - 2013/1/1

Y1 - 2013/1/1

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