title: Sex differences in the regulation of spatially distinct cardiac mitochondrial subpopulations.
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 Ca(2+) retention capacity compared with SSM, however, there was a greater sensitivity to Ca(2+)-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.
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil. rogeriofaustinoribeiro@hotmail.com.
authors.forename: Eduardo
authors.identifier: 0000-0002-9725-3869
authors.lastname: Hertel Ribeiro
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Karoline Sousa
authors.initials: KS
authors.lastname: Ronconi
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Elis Aguiar
authors.initials: EA
authors.lastname: Morra
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Patrícia Ribeiro
authors.initials: PR
authors.lastname: Do Val Lima
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Marcella Leite
authors.initials: ML
authors.lastname: Porto
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Dalton Valentim
authors.initials: DV
authors.lastname: Vassallo
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Suely Gomes
authors.initials: SG
authors.lastname: Figueiredo
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors.forename: Ivanita
authors.initials: I
authors.lastname: Stefanon
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005260:Female; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D010085:Oxidative Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D000244:Adenosine Diphosphate; D002118:Calcium
keywords: Heart; Mitochondria; Mitochondrial subpopulations; Sex differences