Target type: biologicalprocess
The process of directing proteins towards and into the mitochondrion, usually mediated by mitochondrial proteins that recognize signals contained within the imported protein. [GOC:mcc, ISBN:0716731363]
Mitochondrial protein targeting is a complex process that ensures the delivery of newly synthesized proteins to their correct location within the mitochondrion. This organelle, responsible for cellular respiration, is composed of two membranes: the outer mitochondrial membrane (OMM) and the inner mitochondrial membrane (IMM), creating an intermembrane space between them. The mitochondrial matrix, the compartment enclosed by the IMM, houses essential enzymes involved in the Krebs cycle and oxidative phosphorylation.
Proteins destined for the mitochondrion contain specific targeting signals called mitochondrial targeting sequences (MTS), which are typically located at their N-terminus. These MTS are amphipathic, with both hydrophobic and hydrophilic residues, and are recognized by a complex of chaperone proteins in the cytosol.
The journey begins with the import of proteins into the mitochondrial matrix. This process is facilitated by the translocase of the outer membrane (TOM) complex, which acts as a gatekeeper for protein entry into the mitochondrion. The MTS interacts with receptors within the TOM complex, triggering protein translocation across the OMM.
Once inside the intermembrane space, the protein encounters the translocase of the inner membrane (TIM) complex, a multi-protein assembly responsible for transporting proteins across the IMM. The TIM complex is a multifaceted entity, with different sub-complexes facilitating the import of different types of proteins. TIM23, for example, plays a crucial role in transporting proteins to the matrix.
The import process is driven by the electrochemical gradient across the IMM, which is maintained by the proton pump embedded in the membrane. This gradient provides the energy for protein translocation into the matrix. As the protein translocates through the TIM complex, the MTS is cleaved by a matrix-localized peptidase, signaling that the protein has reached its final destination.
While many proteins remain in the matrix, some are further targeted to the IMM, the intermembrane space, or the outer membrane. These proteins contain additional targeting signals that direct them to their specific location. For example, proteins destined for the IMM possess internal targeting sequences recognized by a distinct TIM complex, TIM22, which facilitates their insertion into the membrane.
Importantly, mitochondrial protein targeting is a highly regulated process, ensuring that only the correct proteins are imported. This is achieved through the interplay of chaperones, targeting signals, and translocases. Chaperone proteins maintain proteins in an unfolded state during transport, preventing aggregation and facilitating efficient translocation. The precise targeting signals within each protein dictate their destination within the mitochondrion.
Overall, mitochondrial protein targeting is a complex and essential process for mitochondrial function. It ensures the efficient delivery of proteins to their correct locations, facilitating the intricate biochemical reactions that power cellular life.
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Protein | Definition | Taxonomy |
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BH3-interacting domain death agonist | A BH3-interacting domain death agonist that is encoded in the genome of human. [PRO:WCB, UniProtKB:P55957] | Homo sapiens (human) |
Translocator protein | [no definition available] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
pk 11195 | PK-11195 : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 1-(2-chlorophenyl)isoquinoline-3-carboxylic acid with the amino group of sec-butylmethylamine | aromatic amide; isoquinolines; monocarboxylic acid amide; monochlorobenzenes | antineoplastic agent |
ro 5-4864 | 4'-chlorodiazepam: selectively binds peripheral benzodiazepine receptor | ||
clonazepam | clonazepam : 1,3-Dihydro-2H-1,4-benzodiazepin-2-one in which the hydrogens at positions 5 and 7 are substituted by 2-chlorophenyl and nitro groups, respectively. It is used in the treatment of all types of epilepsy and seizures, as well as myoclonus and associated abnormal movements, and panic disorders. However, its use can be limited by the development of tolerance and by sedation. Clonazepam: An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of GAMMA-AMINOBUTYRIC ACID receptor responses. | 1,4-benzodiazepinone; monochlorobenzenes | anticonvulsant; anxiolytic drug; GABA modulator |
nordazepam | nordazepam : A 1,4-benzodiazepinone having phenyl and chloro substituents at positions 5 and 7 respectively; it has anticonvulsant, anxiolytic, muscle relaxant and sedative properties but is used primarily in the treatment of anxiety. Nordazepam: An intermediate in the metabolism of DIAZEPAM to OXAZEPAM. It may have actions similar to those of diazepam. | 1,4-benzodiazepinone; organochlorine compound | anticonvulsant; anxiolytic drug; GABA modulator; human metabolite; sedative |
diazepam | diazepam : A 1,4-benzodiazepinone that is 1,3-dihydro-2H-1,4-benzodiazepin-2-one substituted by a chloro group at position 7, a methyl group at position 1 and a phenyl group at position 5. Diazepam: A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity. | 1,4-benzodiazepinone; organochlorine compound | anticonvulsant; anxiolytic drug; environmental contaminant; sedative; xenobiotic |
flunitrazepam | flunitrazepam : A 1,4-benzodiazepinone that is nitrazepam substituted by a methyl group at position 1 and by a fluoro group at position 2'. It is a potent hypnotic, sedative, and amnestic drug used to treat chronic insomnia. Flunitrazepam: A benzodiazepine with pharmacologic actions similar to those of DIAZEPAM that can cause ANTEROGRADE AMNESIA. Some reports indicate that it is used as a date rape drug and suggest that it may precipitate violent behavior. The United States Government has banned the importation of this drug. | 1,4-benzodiazepinone; C-nitro compound; monofluorobenzenes | anxiolytic drug; GABAA receptor agonist; sedative |
gossypol | Gossypol: A dimeric sesquiterpene found in cottonseed (GOSSYPIUM). The (-) isomer is active as a male contraceptive (CONTRACEPTIVE AGENTS, MALE) whereas toxic symptoms are associated with the (+) isomer. | ||
lorazepam | Lorazepam: A benzodiazepine used as an anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent. | benzodiazepine | |
nitrazepam | nitrazepam : A 1,4-benzodiazepinone that is 1,3-dihydro-2H-1,4-benzodiazepin-2-one which is substituted at positions 5 and 7 by phenyl and nitro groups, respectively. It is used as a hypnotic for the short-term management of insomnia and for the treatment of epileptic spasms in infants (West's syndrome). Nitrazepam: A benzodiazepine derivative used as an anticonvulsant and hypnotic. | 1,4-benzodiazepinone; C-nitro compound | anticonvulsant; antispasmodic drug; drug metabolite; GABA modulator; sedative |
cm 7116 | norflutoprazepam: structure | benzodiazepine | |
oxazepam | oxazepam : A 1,4-benzodiazepinone that is 1,3-dihydro-2H-1,4-benzodiazepin-2-one substituted by a chloro group at position 7, a hydroxy group at position 3 and phenyl group at position 5. Oxazepam: A benzodiazepine used in the treatment of anxiety, alcohol withdrawal, and insomnia. | 1,4-benzodiazepinone; organochlorine compound | anxiolytic drug; environmental contaminant; xenobiotic |
temazepam | Temazepam: A benzodiazepine that acts as a GAMMA-AMINOBUTYRIC ACID modulator and anti-anxiety agent. | benzodiazepine | |
chlordesmethyldiazepam | benzodiazepine | ||
halazepam | halazepam: structure | organic molecular entity | |
alpidem | imidazoles | ||
epigallocatechin gallate | (-)-epigallocatechin 3-gallate : A gallate ester obtained by the formal condensation of gallic acid with the (3R)-hydroxy group of (-)-epigallocatechin. epigallocatechin gallate: a steroid 5alpha-reductase inhibitor and antimutagen in green tea (Camellia sinensis) | flavans; gallate ester; polyphenol | antineoplastic agent; antioxidant; apoptosis inducer; geroprotector; Hsp90 inhibitor; neuroprotective agent; plant metabolite |
n-desmethylflunitrazepam | |||
7-aminonitrazepam | 7-aminonitrazepam: urinary metabolite of nitrazepam | benzodiazepine | |
ro 20-1815 | 7-aminoflunitrazepam: flunitrazepam metabolite; structure given in first source | benzodiazepine | |
dx 9065 | |||
ro 11-6893 | Ro 11-6893: RN given refers to (R)-isomer | ||
n,n-di-n-hexyl-2-(4-fluorophenyl)indole-3-acetamide | N,N-di-n-hexyl-2-(4-fluorophenyl)indole-3-acetamide: binds with high affinity to glial mitochondrial diazepam binding inhibitor receptors & increases mitochondrial steroidogenesis | phenylindole | |
6-n-tridecylsalicylic acid | 6-n-tridecylsalicylic acid: structure given in first source | hydroxybenzoic acid | |
7-aminoclonazepam | benzodiazepine | ||
ro 5-3438 | Ro 5-3438: structure | ||
n-desmethylflunitrazepam | N-desmethylflunitrazepam: metabolite of flunitrazepam | ||
ro 05-4082 | ID 690: methyl deriv of clonazepam; structure | ||
5,6-dehydrokawain | 5,6-dehydrokawain: from Alpinia speciosa rhizoma; RN given for cpd without isomeric designation; structure given in first source | 2-pyranones; aromatic ether | |
ac-5216 | |||
cb 34 | CB 34: ligand for peripheral benzodiazepine receptors; structure in first source | ||
n-(2-methoxybenzyl)-n-(4-phenoxypyridin-3-yl)acetamide | N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide: for imaging brain peripheral benzodiazepine receptors; structure in first source | ||
ssr180575 | SSR180575: structure in first source | ||
daa 1106 | |||
abt-737 | aromatic amine; aryl sulfide; biphenyls; C-nitro compound; monochlorobenzenes; N-arylpiperazine; N-sulfonylcarboxamide; secondary amino compound; tertiary amino compound | anti-allergic agent; anti-inflammatory agent; antineoplastic agent; apoptosis inducer; B-cell lymphoma 2 inhibitor | |
naluzotan | naluzotan: an antidepressant and anti-anxiety agent; structure in first source | ||
dpa-713 | |||
a 803467 | A 803467: an Nav1.8 sodium channel blocker; structure in first source | ||
n-fluoroacetyl-n-(2,5-dimethoxybenzyl)-2-phenoxyaniline | N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline: a peripheral benzodiazepine receptor PET ligand; structure in first source | ||
meiogynin a | meiogynin A: from the bark of Meiogyne cylindrocarpa; structure in first source | ||
MS-417 | MS-417 : A member of the class of thienotriazolodiazepines that is the methyl ester of [(6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetic acid. A bromodomain and extra-terminal domain (BET)-specific inhibitor that belongs to a group of thienodiazepine-based compounds | methyl ester; monochlorobenzenes; thienotriazolodiazepine | |
apogossypolone | apogossypolone: has antineoplastic activity; structure in first source |