title: Chronic expression of RCAN1-1L protein induces mitochondrial autophagy and metabolic shift from oxidative phosphorylation to glycolysis in neuronal cells.
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. We identify 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.
authors.affiliation: Ethel Percy Andrus Gerontology Center of the Davis School of Gerontology and the Division of Molecular and Computational Biology, Department of Biological Sciences, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, California 90089-0191, USA.
authors.forename: Gennady
authors.initials: G
authors.lastname: Ermak
authors.forename: Sonal
authors.initials: S
authors.lastname: Sojitra
authors.forename: Fei
authors.initials: F
authors.lastname: Yin
authors.forename: Enrique
authors.initials: E
authors.lastname: Cadenas
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Cuervo
authors.forename: Kelvin J A
authors.initials: KJ
authors.lastname: Davies
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D016923:Cell Death; D002469:Cell Separation; D002470:Cell Survival; D004268:DNA-Binding Proteins; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D006019:Glycolysis; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009124:Muscle Proteins / Q000096:biosynthesis*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats
chemical_list: D033741:Adenine Nucleotide Translocator 1; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C108612:RCAN1 protein, human; C548050:RCAN1 protein, rat; D010100:Oxygen