TY - JOUR
AU - Chiu, Haw-Jyh
AU - Fischman, Donald A.
AU - Hammerling, Ulrich
TI - Vitamin A depletion causes oxidative stress, mitochondrial dysfunction, and PARP-1-dependent energy deprivation
JO - The FASEB Journal
JA - The FASEB Journal
VL - 22
IS - 11
SN - 0892-6638
UR - https://doi.org/10.1096/fj.08-112375
DO - https://doi.org/10.1096/fj.08-112375
SP - 3878
EP - 3887
KW - lymphocytes
KW - mitochondrion
KW - reactive oxygen species
KW - bioenergetics
PY - 2008
AB - 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 Adeprivation 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. FASEB J. 22, 3878?3887 (2008)
ER -