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Literature summary for 1.1.99.1 extracted from

  • Park, S.; Choi, S.G.; Yoo, S.M.; Son, J.H.; Jung, Y.K.
    Choline dehydrogenase interacts with SQSTM1/p62 to recruit LC3 and stimulate mitophagy (2014), Autophagy, 10, 1906-1920 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
gene CHDH, recombinant expression of wild-type and truncated mutant enzymes, enzyme overexpression in HeLa cells Homo sapiens

Protein Variants

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

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
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Natural Substrates/ Products (Substrates)

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

Organism UniProt Comment Textmining
Homo sapiens Q8NE62
-
-
Mus musculus Q8BJ64
-
-

Source Tissue

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 and Products (Substrate)

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

Synonyms Comment Organism
Cdh
-
Mus musculus
CHDH
-
Homo sapiens
CHDH
-
Mus musculus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
assay at Homo sapiens

Cofactor

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

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