Endocrine Abstracts

Appreciation of hormonal control over mitochondrial function has increased over recent decades. Mitochondria adapt to the cellular environment through a variety of mechanisms; mitochondrial dynamics (fusion, fission, transfer) or through the signalling of a variety of proteins to induce mitophagy, depending on the cell stressor. In parallel, nuclear receptors and the production of their steroid hormone ligands within mitochondria have been a reoccurring incidental measurement. This is of interest as glucocorticoids such as dexamethasone and sex hormones such as progesterone have been linked to mitochondrial fusion and mitophagy, but the mechanisms remain largely unknown. Our study highlights a nuclear-mitochondrial phenomenon whereby nuclear receptors are located inside mitochondria along with steroidogenic enzymes. Our study examines over 20 mitochondrial proteomics datasets and identifies a cohort of proteins including glucocorticoid, androgen, and estrogen receptors, and steroidogenic enzymes, an important observation as the mitochondria are responsible for the biosynthesis of many steroid hormones including aldosterone and pregnenolone through P450scc (cholesterol side-chain cleavage). We have investigated the localisation of these proteins to the mitochondria with Western Blotting and high-resolution imaging techniques (NanoLive, confocal, epifluorescence) using live and fixed cells and a variety of cell lines including adipocytes, skeletal muscle, neuronal and cardiovascular cells. We postulate the existence of a novel signalling axis that recruits conventionally nuclear-located endocrine responses to mitochondria.