Cloned (Comment) | Organism |
---|---|
gene CHDH, recombinant expression of wild-type and truncated mutant enzymes, enzyme overexpression in HeLa cells | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | construction of a series of CHDH deletion mutants in HeLa cells. Overexpression of the CHDH-RDDELTA or CHDHFB2DELTA mutants induces colocalization of GFP-LC3 with Mito-RFP as effectively as wild-type CHDH, but the CHDH-FB1DELTA mutant fails to do so. Knockdown of CHDH expression impairs CCCP-induced mitophagy and PARK2/parkin-mediated clearance of mitochondria in mammalian cells, including HeLa cells. Conversely, overexpression of CHDH accelerates PARK2-mediated mitophagy. Overexpression of the FB1 domain only in cytosol reduces CCCP-induced mitochondrial degradation via competitive interaction with SQSTM1 | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
mitochondrial membrane | - |
Mus musculus | 31966 | - |
mitochondrial membrane | CHDH appears to have a mitochondria-targeting sequence at its N-terminus (residues 1 to 38). CHDH is found on both the outer and inner membranes of mitochondria in resting cells. Upon induction of mitophagy, CHDH accumulates on the outer membrane in a mitochondrial potential-dependent manner. CHDH accumulates on the outer membrane following mitochondrial damage. Topology of CHDH in the mitochondrial membrane and mechanism by which CHDH translocates across the mitochondrial membranes, overview | Homo sapiens | 31966 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
choline + acceptor | Homo sapiens | - |
betaine aldehyde + reduced acceptor | - |
r | |
choline + acceptor | Mus musculus | - |
betaine aldehyde + reduced acceptor | - |
r |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q8NE62 | - |
- |
Mus musculus | Q8BJ64 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
HEK-293T cell | - |
Homo sapiens | - |
HeLa cell | - |
Homo sapiens | - |
neuronal cell | - |
Mus musculus | - |
SN4741 cell | dopaminergic cells | Mus musculus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
choline + acceptor | - |
Homo sapiens | betaine aldehyde + reduced acceptor | - |
r | |
choline + acceptor | - |
Mus musculus | betaine aldehyde + reduced acceptor | - |
r |
Synonyms | Comment | Organism |
---|---|---|
Cdh | - |
Mus musculus |
CHDH | - |
Homo sapiens |
CHDH | - |
Mus musculus |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
8 | - |
assay at | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
additional information | the enzyme has 3 functional domains, named FAD/NAD(P)-binding domain 1 (FB1, residues 39 to 326), FAD-linked reductase domain (RD, residues 333 to 515) and FAD/NAD(P)-binding domain 2 (FB2, residues 511 to 574) | Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | downregulation of CHDH expression abolishes the colocalization of MAP1LC3B/LC3B (LC3) with mitochondria | Mus musculus |
malfunction | knockdown of CHDH expression impairs CCCP-induced mitophagy and PARK2/parkin-mediated clearance of mitochondria in mammalian cells, including HeLa cells. Conversely, overexpression of CHDH accelerates PARK2-mediated mitophagy | Homo sapiens |
additional information | CHDH appears to have a mitochondria-targeting sequence at its N-terminus (residues 1 to 38) and 3 functional domains, named FAD/NAD(P)-binding domain 1 (FB1, residues 39 to 326), FAD-linked reductase domain (RD, residues 333 to 515) and FAD/NAD(P)-binding domain 2 (FB2, residues 511 to 574) | Homo sapiens |
physiological function | in SN4741 dopaminergic cells, CHDH plays a role during mitophagy triggered by 1-methyl-4-phenylpyridinium (MPPC), a Parkinsonism-causing reagent. Like CCCP, treatment with MPPC induces a significant level (30.0%) of colocalization of MAP1LC3B/LC3B (LC3) with mitochondria in SN4741 cells. CHDH is essential in the mitophagy of SN4741 dopaminergic neurons following exposure to MPPC | Mus musculus |
physiological function | pivotal role of CHDH in mitophagy. CHDH is required for mitophagy in which CHDH interacts with SQSTM1, a mitophagic adaptor molecule, and subsequently facilitates the recruitment of MAP1LC3B/LC3B (LC3) into the mitochondria. CHDH is not a substrate of PARK2 but interacts with SQSTM1 independently of PARK2 to recruit SQSTM1 into depolarized mitochondria. The FB1 domain of CHDH is exposed to the cytosol and is required for the interaction with SQSTM1, and overexpression of the FB1 domain only in cytosol reduces CCCP-induced mitochondrial degradation via competitive interaction with SQSTM1. CHDH is required for PARK2-mediated mitophagy for the recruitment of SQSTM1 and LC3 onto the mitochondria for cargo recognition. CHDH overexpression enhances CCCP-induced clearance of mitochondria. But the expression level of CHDH does not affect the stability of PINK1 protein, although CCCP treatment stabilizes PINK1 in mitochondria. Mitophagic activity of CHDH is independent of CDH enzyme activity | Homo sapiens |