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Inner mitochondrial translocase Tim50 is central in steroid metabolism in steroidogenic tissues
Author(s) -
Bose Himangshu S,
Marshall Brendan,
Perry Elizabeth W,
Whittal Randy M
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.660.3
Subject(s) - pregnenolone , cholesterol side chain cleavage enzyme , mitochondrion , translocase , inner mitochondrial membrane , amino acid , biology , biochemistry , microbiology and biotechnology , mitochondrial matrix , metabolism , enzyme , cytochrome p450 , chemistry , steroid , gene , hormone , cytosol , chromosomal translocation
Steroid hormones are synthesized in an acute condition but some genes are also transcriptionally active, and they are essential for survival of all mammals. The synthesis of metabolic reaction is initiated in the matrix side of mitochondria. In addition to the presence of different enzymes mitochondria has many translocases, which help in sorting and localization proteins across the subcompartments. The molecular basis of mitochondrial redistribution depends on the different steps of protein folding. In adrenal and gonads, Cytochrome P450 side chain cleavage enzyme (SCC or CYP11A1), catalyzes cholesterol to pregnenolone. We find that gradual mitochondrial import of SCC led to the association with mitochondrial translocase, Tim50. The N‐terminal is cleaved first followed by the C‐terminus amino acids, where deletion of more than ten amino acids from the C‐terminus reduced the activity and interaction with Tim50. Similarly, knocking down Tim50 ablates SCC activity and blocking complete SCC import into the inter mitochondrial membrane ablated activity. These two proteins are colocalized in the mitochondria, where amino acids 208–212 of Tim50 first interact with SCC. A mutation in either of these two proteins reduced their interaction, resulting in a metabolic and developmental disorder. Thus, the metabolism for conversion of pregnenolone depends on SCC and Tim50 together, as the negative feedback is inhibited in the absence of interaction between these two proteins, increasing ACTH levels. Support or Funding Information No This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .