Steroid hormone synthesis in mitochondria.
Level 5 - mechanism / opinion, no new human data
Narrative review of biochemical mechanisms without empirical clinical trial data
PubMed 23628605 · doi:10.1016/j.mce.2013.04.014
What was done
Narrative review describing the enzymatic pathways, electron-transfer systems, and multi-protein transport complexes mediating steroid hormone and vitamin D biosynthesis in mitochondria.
What was found
The abstract reports no quantitative data. It describes that mitochondria in steroidogenic cells (adrenal, gonad, placenta, brain) contain the cholesterol side-chain cleavage enzyme (P450scc) and electron-transfer partners (ferredoxin reductase, ferredoxin), which convert cholesterol to pregnenolone to chronically regulate steroidogenesis. Additional mitochondrial enzymes include 3β-hydroxysteroid dehydrogenase, 11β-hydroxylase, aldosterone synthase, and renal vitamin D-metabolizing enzymes. Acute regulation is driven by steroidogenic acute regulatory protein (StAR) interacting with an outer mitochondrial membrane complex containing TSPO (18 kDa), VDAC-1, PAP7 (ACBD3), and PKAR1A. Human deficiency diseases have been identified for StAR and all mitochondrial steroidogenic enzymes, but not for electron-transfer proteins or the cholesterol import machine.
Why it matters
It summarizes the molecular architecture required for mitochondrial steroidogenesis and distinguishes pathway components that cause known human deficiency disorders from those that do not.
Limits
As a narrative review, it presents no primary clinical data, quantitative effect estimates, or sample sizes. The exact mechanism by which the outer-membrane protein complex loads and delivers cholesterol to P450scc remains undetermined.
Cited by
- supports Steroid hormone biosynthesis takes place inside the mitochondria.