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Title of Journal: J Bioenerg Biomembr

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Abbravation: Journal of Bioenergetics and Biomembranes

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Springer US

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DOI

10.1007/s12614-014-2096-2

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1573-6881

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Sex dependent alterations in mitochondrial electro

Authors: T G Demarest R A Schuh E L Waite J Waddell M C McKenna Gary Fiskum
Publish Date: 2016/09/28
Volume: 48, Issue: 6, Pages: 591-598
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Abstract

Males are more susceptible to brain mitochondrial bioenergetic dysfunction following neonatal cerebral hypoxicischemia HI than females Mitochondrial biogenesis has been implicated in the cellular response to HI injury but sex differences in biogenesis following HI have not been described We tested the hypothesis that mitochondrial biogenesis or the expression of mitochondrial electron transport chain ETC proteins are differentially stimulated in the brains of 8 day old male and female rats one day following HI and promoted by treatment with acetylLcarnitine ALCAR There were no sex differences in mitochondrial mass as reflected by the ratio of mitochondrial to nuclear DNA mtDNA/nDNA and citrate synthase enzyme activity present one day following HI or sham surgery There was an increase in mtDNA/nDNA however in the hypoxic and ischemic ipsilateral hemisphere after HI in both male and female brains at one day postinjury which was suppressed by ALCAR Citrate synthase activity was increased in the ipsilateral hemisphere of ALCAR treated male and female brain Most importantly the levels of representative mitochondrial proteins present in ETC complexes I II and IV increased substantially one day following HI in female but not male brain This sex difference is consistent with the increase in the mitochondrial biogenesisassociated transcription factor NRF2/GABPα following HI in females in contrast to the decrease observed with males In conclusion the female sexselective increase in ETC proteins following HI may at least partially explain the relative female resilience to mitochondrial respiratory impairment and neuronal death that occur after HIAll authors were directly involved in the design or conduct of the study and contributed to the writing/editing of the manuscript TGD was responsible for data collection analysis interpretation and manuscript/figure preparation RAS and ELW assisted in data collection JW performed all surgeries and drug treatments GF and MCM were responsible for experimental design and interpretation of results

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