Vitamin A depletion causes oxidative stress, mitochondrial dysfunction, and PARP-1-dependent energy deprivation

A significant unresolved question is how vitamin A deprivation causes, and why retinoic acid fails to reverse, immunodeficiency. When depleted of vitamin A, T cells undergo programmed cell death (PCD), which is enhanced by the natural competitor of retinol, anhydroretinol. PCD does not happen by apo...

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Bibliographic Details
Published in:The FASEB journal 2008-11, Vol.22 (11), p.3878-3887
Main Authors: Chiu, Haw-Jyh, Fischman, Donald A, Hammerling, Ulrich
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Animals
Apoptosis
bioenergetics
Cell Hypoxia
DNA Fragmentation
Energy Metabolism
Enzyme Activation
Homeostasis
Humans
Jurkat Cells
lymphocytes
Mice
Mice, Knockout
Mitochondria - metabolism
Mitochondria - pathology
mitochondrion
NAD - metabolism
Oxidative Stress
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerases - genetics
Poly(ADP-ribose) Polymerases - metabolism
reactive oxygen species
Reactive Oxygen Species - metabolism
Research Communications
Vitamin A - metabolism
Vitamin A Deficiency - enzymology
Vitamin A Deficiency - pathology
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Summary:A significant unresolved question is how vitamin A deprivation causes, and why retinoic acid fails to reverse, immunodeficiency. When depleted of vitamin A, T cells undergo programmed cell death (PCD), which is enhanced by the natural competitor of retinol, anhydroretinol. PCD does not happen by apoptosis, despite the occurrence of shared early events, including mitochondrial membrane depolarization, permeability transition pore opening, and cytochrome c release. It also lacks caspase-3 activation, chromatin condensation, and endonuclease-mediated DNA degradation, hallmarks of apoptosis. PCD following vitamin A deprivation exhibits increased production of reactive oxygen species (ROS), drastic reductions in ATP and NAD⁺ levels, and activation of poly-(ADP-ribose) polymerase (PARP) -1. These latter steps are causative because neutralizing ROS, imposing hypoxic conditions, or inhibiting PARP-1 by genetic or pharmacologic approaches prevents energy depletion and PCD. The data highlight a novel regulatory role of vitamin A in mitochondrial energy homeostasis.--Chiu, H.-J., Fischman, D. A., Hammerling, U. Vitamin A depletion causes oxidative stress, mitochondrial dysfunction, and PARP-1-dependent energy deprivation.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.08-112375