Mitochondria in neurodegenerative disorders: regulation  of the redox state and death signaling leading  to neuronal death and survival.
In Parkinson's disease, impaired function of mitochondrial complex I is involved in selective degeneration of dopamine neurons in the substantia nigra. Mitochondria are now considered to play an active role in neuronal death process through activating "intrinsic" apoptotic signaling, in addition to production of reactive oxygen species. This paper presents our recent findings on new functions of mitochondria in regulation of their redox state and function through reversible "S-glutathionylation", a mixed disulfide binding between sulfhydryl groups of GSH and protein cysteine in complex I subunits. Type A monoamine oxidase (MAO-A) localized at the mitochondrial outer membrane is a binding site of neurotoxins leading to apoptosis. Rasagiline and (-)deprenyl, type B MAO inhibitors of propagylamine-derivatives, bind to MAO-A to protect neuronal cells against apoptosis through induction of pro-survival Bcl-2 and neurotrophic factors. This review discusses the new role of mitochondria in regulation of neuronal cell death of neurodegenerative disorders.
Naoi
Makoto
M
Department of Neurosciences, Gifu International Institute of Biotechnology, Kakamigahara, Gifu, Japan. mnaoi@giib.or.jp
Maruyama
Wakako
W
Yi
Hong
H
Inaba
Keiko
K
Akao
Yukihiro
Y
Shamoto-Nagai
Masayo
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008995:Monoamine Oxidase / Q000187:drug effects / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase; D005978:Glutathione