negative regulation of mitochondrial membrane permeability
Definition
Target type: biologicalprocess
Any process that decreases the frequency, rate or extent of the passage or uptake of molecules by the mitochondrial membrane. [PMID:10781072]
Negative regulation of mitochondrial membrane permeability is a crucial process that safeguards the integrity of the mitochondria and prevents the release of pro-apoptotic factors into the cytosol. It involves a delicate balance of proteins and mechanisms that control the permeability of the outer mitochondrial membrane (OMM) and the inner mitochondrial membrane (IMM).
The OMM is a porous membrane that typically allows the passage of small molecules and ions. However, during stress or apoptotic stimuli, the permeability of the OMM can increase, leading to the release of pro-apoptotic proteins such as cytochrome c and apoptosis-inducing factor (AIF). This release initiates a cascade of events that ultimately leads to programmed cell death.
The IMM is the innermost membrane of the mitochondria, and it plays a key role in the electron transport chain and ATP production. Its permeability is tightly regulated by the mitochondrial permeability transition pore (mPTP), a multi-protein complex that can open under specific conditions.
Several mechanisms contribute to negative regulation of mitochondrial membrane permeability:
1. **Anti-apoptotic proteins**: These proteins, such as Bcl-2 and Bcl-xL, can bind to pro-apoptotic proteins, such as Bax and Bak, preventing their oligomerization and insertion into the OMM. This inhibition prevents the formation of pores in the OMM and subsequent release of pro-apoptotic proteins.
2. **Mitochondrial chaperones**: Proteins like Hsp70 and Hsp90 assist in protein folding and prevent the aggregation of unfolded proteins, which can trigger apoptosis.
3. **Regulation of mPTP**: Several factors influence the opening of the mPTP, including calcium levels, reactive oxygen species (ROS), and ATP levels. Negative regulation of mPTP involves maintaining these factors within specific ranges, preventing its opening and the release of pro-apoptotic molecules.
4. **Mitochondrial fission and fusion**: The dynamic processes of mitochondrial fission and fusion help maintain mitochondrial health. Fission allows for the removal of damaged mitochondria, while fusion allows for the exchange of healthy components between mitochondria.
5. **Autophagy**: This process involves the degradation of damaged mitochondria, preventing the release of pro-apoptotic factors.
In summary, negative regulation of mitochondrial membrane permeability is a complex process that involves a network of proteins and mechanisms that prevent the uncontrolled release of pro-apoptotic factors. This regulation is essential for maintaining mitochondrial integrity and preventing cell death. Dysregulation of these processes can lead to various diseases, including neurodegenerative disorders and cancer.'
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Proteins (2)
| Protein | Definition | Taxonomy |
|---|---|---|
| Bcl-2-like protein 2 | A protein that is a translation product of any of the following genes in human | Homo sapiens (human) |
| Hexokinase-2 | A hexokinase-2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P52789] | Homo sapiens (human) |
Compounds (12)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| benserazide | benserazide : A carbohydrazide that results from the formal condensation of the carboxy group of DL-serine with the primary amino group of 4-(hydrazinylmethyl)benzene-1,2,3-triol. An aromatic-L-amino-acid decarboxylase inhibitor (DOPA decarboxylase inhibitor) that does not enter the central nervous system, it is used as its hydrochloride salt as an adjunct to levodopa in the treatment of parkinsonism. By preventing the conversion of levodopa to dopamine in the periphery, it causes an increase in the amount of levodopa reaching the central nervous system and so reduces the required dose. Benserazide has no antiparkinson actions when given alone. Benserazide: An inhibitor of DOPA DECARBOXYLASE that does not enter the central nervous system. It is often given with LEVODOPA in the treatment of parkinsonism to prevent the conversion of levodopa to dopamine in the periphery, thereby increasing the amount that reaches the central nervous system and reducing the required dose. It has no antiparkinson actions when given alone. | carbohydrazide; catechols; primary alcohol; primary amino compound | antiparkinson drug; dopaminergic agent; EC 4.1.1.28 (aromatic-L-amino-acid decarboxylase) inhibitor |
| 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. | ||
| 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 |
| chelerythrine chloride | |||
| blastmycin | blastmycin: structure | amidobenzoic acid | |
| apogossypol | apogossypol: structure in first source | ||
| umi-77 | UMI-77: an Mcl-1 inhibitor; structure in first source | ||
| andrographolide | carbobicyclic compound; gamma-lactone; labdane diterpenoid; primary alcohol; secondary alcohol | anti-HIV agent; anti-inflammatory drug; antineoplastic agent; metabolite | |
| 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 | |
| navitoclax | aryl sulfide; monochlorobenzenes; morpholines; N-sulfonylcarboxamide; organofluorine compound; piperazines; secondary amino compound; sulfone; tertiary amino compound | antineoplastic agent; apoptosis inducer; B-cell lymphoma 2 inhibitor | |
| abt-199 | venetoclax : A member of the class of pyrrolopyridines that is a potent inhibitor of the antiapoptotic protein B-cell lymphoma 2. It is used for treamtment of chronic lymphocytic leukemia with 17p deletion. venetoclax: A BCL-2 inhibitor with antineoplastic activity that is used in the treatment of CHRONIC LYMPHOCYTIC LEUKEMIA associated with chromosome 17p deletion; structure in first source. | aromatic ether; C-nitro compound; monochlorobenzenes; N-alkylpiperazine; N-arylpiperazine; N-sulfonylcarboxamide; oxanes; pyrrolopyridine | antineoplastic agent; apoptosis inducer; B-cell lymphoma 2 inhibitor |
| a-1155463 | A-1155463: a Bcl-X(L) inhibitor; structure in first source |