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Sex differences in the regulation of spatially distinct cardiac mitochondrial subpopulations

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Abstract

Spatially distinct mitochondrial subpopulation may mediate myocardial pathology through permeability transition pore opening (MPTP). The goal of this study was to assess sex differences on the two spatially distinct mitochondrial subpopulations: subsarcolemmal mitochondria (SSM) and intermyofibrillar mitochondria (IFM) based on morphology, membrane potential, mitochondrial function, oxidative phosphorylation, and MPTP. Aged matched Wistar rats were used to study SSM and IFM. Mitochondrial size was larger in SSM than in IFM in both genders. However, SSM internal complexity, yield, and membrane potential were higher in male than in female. The maximal rate of mitochondrial respiration, states 3 and 4, using glutamate + malate as substrate, were higher in IFM and SSM in the male group compared to female. The respiratory control ratio (RCR—state3/state 4), was not different in both SSM and IFM with glutamate + malate. The ADP:O ratio was found higher in IFM and SSM from female compared to males. When pyruvate was used, state 3 was found unchanged in both IFM and SSM, state 4 was also greater in male IFM compared to female. The RCR increased in the SSM while IFM remained the same. State 4 was higher in male SSM while in the IFM remained the same. The IFM presented a higher Ca2+ retention capacity compared with SSM, however, there was a greater sensitivity to Ca2+-induced MPTP in SSM and IFM in the male group compared to female. In conclusion, our data show that spatially distinct mitochondrial subpopulations have sex-based differences in oxidative phosphorylation, morphology, and calcium retention capacity.

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Author contribution

Rogério Faustino Ribeiro Júnior, Karoline de Sousa Ronconi, Elis Morra, Patricia Ribeiro do Val Lima and Marcella Leite Porto performed the experiments, analyzed the data, discussed the results, and wrote the paper, Suely Gomes Figueiredo, Dalton Valentim Vassallo, and Ivanita Stefanon were involved in discussing the results and writing the paper.

Funding

This study was supported by Grants from CAPES; CNPq (470479-2013-2), CNPq (455294/2014-3); and FAPES. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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  1. Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil

    Rogério Faustino Ribeiro Jr., Karoline Sousa Ronconi, Elis Aguiar Morra, Patrícia Ribeiro Do Val Lima, Marcella Leite Porto, Dalton Valentim Vassallo, Suely Gomes Figueiredo & Ivanita Stefanon

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  1. Rogério Faustino Ribeiro Jr.
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  2. Karoline Sousa Ronconi
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Correspondence to Rogério Faustino Ribeiro Jr..

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Ribeiro, R.F., Ronconi, K.S., Morra, E.A. et al. Sex differences in the regulation of spatially distinct cardiac mitochondrial subpopulations. Mol Cell Biochem 419, 41–51 (2016). https://doi.org/10.1007/s11010-016-2748-4

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