Glucocorticoids are involved in stress regulation and produce their actions via the glucocorticoid receptor, a nuclear transcription factor. The glucocorticoid receptor is translocated from the cytosol to the mitochondria where corticosteroids have a direct influence on mitochondrially transcribed mRNA (mtDNA) and mitochondrial physiology.
To determine if stress affects mtRNA expression, the authors exposed rats to both acute and chronic immobilization stress and examined mtRNA expression using quantitative RT-PCR. Acute stress had a main effect on mtRNA expression with expression of NADH dehydrogenase 1, 3, and 6 (ND-1, ND-3, ND-6) and ATP synthase 6 (ATP-6) genes significantly down-regulated. Chronic stress induced a significant up-regulation of ND-6 expression.
Glucocorticoid dependence for this effect was shown by the observation that adrenalectomy abolished acute stress-induced mtRNA regulation. These findings demonstrate glucocorticoid and stress-dependent transcriptional regulation of the mitochondrial genome in vivo and are consistent with previous work linking stress and glucocorticoids with changes in the function of brain mitochondria. The results have application for neurodegenerative disorders in which mitochondrial dysfunction is widely implicated and in which stress can be a contributing factor.
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Hunter RG, Seligsohn M, Rubin TG, Griffiths BB, Ozdemir Y, Pfaff DW, Datson NA, McEwen BS: Stress and corticosteroids regulate rat hippocampal mitochondrial DNA gene expression via the glucocorticoid receptor. Proc. Natl. Acad. Sci. USA [Epub ahead of print, July 25, 2016; doi: 10.1073/pnas.1602185113].
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