Abstract
With the current explosion of knowledge on the role of mitochondrial dysfunction in the genesis of various human disease states, there is an increased interest in targeting mitochondrial processes, pathways, and proteins for drug discovery efforts in cancer and cardiovascular, metabolic, and central nervous system diseases, the latter including autism and neurodegenerative diseases. We provide an update on understanding the central role of the mitochondrion in ATP and reactive oxygen species production and in controlling cell death pathways.
Footnotes
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
ABBREVIATIONS:
- mtDNA
- mitochondrial DNA
- ΔΨm
- mitochondrial membrane potential
- Aβ
- amyloid β peptide
- AD
- Alzheimer's disease
- AIF
- apoptosis-inducing factor
- ALS
- amyotrophic lateral sclerosis
- ANT
- adenine nucleotide translocator
- Bak
- Bcl-2 homologous antagonist killer
- Bax
- proapoptotic Bcl-2-associated X protein
- BcL
- B-cell lymphoma protein
- BH3
- proapopotoic Bcl-2 family members
- CytC
- cytochrome c
- Cyp-D
- cyclophilin D
- DRP1
- dynamin-related protein 1
- ETC
- electron transport chain
- FAD
- flavin adenine dinucleotide
- HD
- Huntington's disease
- IAP
- inhibitor of apoptosis
- IMM
- inner mitochondrial membrane
- MLKL
- mixed lineage kinase-domain-like protein
- MPT
- mitochondrial permeability transition
- MPTP
- MPT pore
- NCE
- new chemical entity
- Nix/BNip3L
- BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like
- nDNA
- nuclear DNA
- NSAID
- nonsteroidal anti-inflammatory drug
- OMM
- outer mitochondrial membrane
- Omi/HtrA2
- homotrimeric serine protease high-temperature requirement A2
- OXPHOS
- oxidative phosphorylation
- PARP
- poly(ADP) ribose polymerase
- PD
- Parkinson's disease
- PGAM5S
- phosphoglycerate mutase/protein phosphatase 5, short form
- PGC-1α
- peroxisome proliferator-activated receptor-γ coactivator 1α
- PKA
- protein kinase A
- RCT
- randomized clinical trial
- ROS
- reactive oxygen species
- RIPK
- receptor interacting protein kinase
- sAC
- soluble adenylyl cyclase
- Smac/DIABLO
- second mitochondria-derived activator of caspases/direct IAP-associated binding protein with low pI
- TNF
- tumor necrosis factor
- TRAF2
- TNF receptor-associated factor 2
- VDAC
- voltage-dependent anion channel
- ABT-737
- 4-{4-[(4′-chlorobiphenyl-2-yl)methyl]piperazin-1-yl}-N-{[4-({(1R)-3-(dimethylamino)-1-[(phenylsulfanyl)methyl]propyl}amino)-3-nitrophenyl]sulfonyl}benzamide
- AT-101
- (−)-1,1′,6,6′,7,7′-hexahydroxy-3,3′-dimethyl-5,5′-bis(1-methylethyl)-[2,2′-binaphthalene]-8,8′-dicarboxaldehyde
- CD437
- 6-(3-(1-adamantyl)-4-hydroxyphenyl)-2-naphthalenecarboxylic acid
- PK 11195
- N-butan-2-yl-1-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide
- ATN-224
- choline tetrathiomolybdate
- STA-4783
- N′1, N′3-dimethyl-N′1, N′3- bis(phenylcarbonothioyl)propanedihydrazide
- PI-H71
- 6-amino-8-[(6-iodo-1,3-benzodioxol-5-yl)thio]-N-(1-methylethyl)-9H-purine-9-propanamine
- KNS-760704
- (R)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine
- CGP 37157
- 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one
- SS-31
- arginyl-2,′6′-dimethyltyrosyl-lysyl-phenylalaninamide
- TRO19622
- (NZ)-N-[(8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-ylidene]hydroxylamine.
- Received January 17, 2012.
- Accepted March 23, 2012.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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