Chronic expression of RCAN1-1L protein induces mitochondrial autophagy and metabolic shift from oxidative phosphorylation to glycolysis in neuronal cells

Gennady Ermak, Sonal Sojitra, Fei Yin, Enrique Cadenas, Ana Maria Cuervo, Kelvin J A Davies

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Expression of the RCAN1 gene can be induced by multiple stresses. RCAN1 proteins (RCAN1s) have both protective and harmful effects and are implicated in common human pathologies. The mechanisms by which RCAN1s function, however, remain poorly understood.Weidentify RCAN1s as regulators of mitochondrial autophagy (mitophagy) and demonstrate that induction of RCAN1-1L can cause dramatic degradation of mitochondria. The mechanisms of such degradation involve the adenine nucleotide translocator and mitochondrial permeability transition pore opening. We also demonstrate that RCAN1-1L induction can shift cellular bioenergetics from aerobic respiration to glycolysis, yet RCAN1-1L has very little effect on cell division, whereas it has a cumulative negative effect on cell survival. These results shed the light on mechanisms by which RCAN1s can protect or harm cells and by which they may operate in human pathologies. They also suggest that RCAN1s are important players in autophagy and such elusive phenomena as the mitochondrial permeability transition pore.

Original languageEnglish (US)
Pages (from-to)14088-14098
Number of pages11
JournalJournal of Biological Chemistry
Volume287
Issue number17
DOIs
StatePublished - Apr 20 2012

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Mitochondrial Proteins
Oxidative Phosphorylation
Autophagy
Pathology
Glycolysis
Cells
Degradation
Mitochondria
Adenine Nucleotides
Cell Division
Energy Metabolism
Cell Survival
Respiration
Genes
Gene Expression
Proteins
mitochondrial permeability transition pore

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Chronic expression of RCAN1-1L protein induces mitochondrial autophagy and metabolic shift from oxidative phosphorylation to glycolysis in neuronal cells. / Ermak, Gennady; Sojitra, Sonal; Yin, Fei; Cadenas, Enrique; Cuervo, Ana Maria; Davies, Kelvin J A.

In: Journal of Biological Chemistry, Vol. 287, No. 17, 20.04.2012, p. 14088-14098.

Research output: Contribution to journalArticle

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AU - Ermak, Gennady

AU - Sojitra, Sonal

AU - Yin, Fei

AU - Cadenas, Enrique

AU - Cuervo, Ana Maria

AU - Davies, Kelvin J A

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AB - Expression of the RCAN1 gene can be induced by multiple stresses. RCAN1 proteins (RCAN1s) have both protective and harmful effects and are implicated in common human pathologies. The mechanisms by which RCAN1s function, however, remain poorly understood.Weidentify RCAN1s as regulators of mitochondrial autophagy (mitophagy) and demonstrate that induction of RCAN1-1L can cause dramatic degradation of mitochondria. The mechanisms of such degradation involve the adenine nucleotide translocator and mitochondrial permeability transition pore opening. We also demonstrate that RCAN1-1L induction can shift cellular bioenergetics from aerobic respiration to glycolysis, yet RCAN1-1L has very little effect on cell division, whereas it has a cumulative negative effect on cell survival. These results shed the light on mechanisms by which RCAN1s can protect or harm cells and by which they may operate in human pathologies. They also suggest that RCAN1s are important players in autophagy and such elusive phenomena as the mitochondrial permeability transition pore.

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