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Mitochondria, mitochondrial diseases and dysfunction and sex differences

Discussion in 'Other Health News and Research' started by pattismith, Nov 10, 2017.

  1. pattismith

    pattismith Senior Member

    some studies about it:

    Gender-specific role of mitochondria in the vulnerability of 6-hydroxydopamine-treated mesencephalic neurons (2010)

    Many neurodegenerative diseases, such as Morbus Parkinson, exhibit a gender-dependency showing a higher incidence in men than women. Most of the neurodegenerative disorders involve either causally or consequently a dysfunction of mitochondria. Therefore, neuronal mitochondria may demonstrate a gender-specificity with respect to structural and functional characteristics of these organelles during toxic and degenerative processes. The application of 6-OHDA (6-hydroxydopamine) in vitro and in vivo represents a well-accepted experimental model of Parkinson's disease causing Parkinsonian symptoms. Besides the known effects of 6-OHDA on mitochondria and neuronal survivability, we aimed to demonstrate that the mitochondrial neurotoxin affects the morphology and survival of primary dopaminergic and non-dopaminergic neurons in the mesencephalon in a gender-specific manner by influencing the transcription of mitochondrial genes, ATP and reactive oxygen species production. Our data suggest that cell death in response to 6-OHDA is primarily caused due to increased oxidative stress which is more pronounced in male than in female mesencephalic neurons.

    Effect of Sex Differences on Brain Mitochondrial Function and Its Suppression by Ovariectomy and in Aged Mice (2015)

    Our results show that young adult females have lower oxidative stress and a higher reduced nicotinamide adenine dinucleotide (NADH)-linked respiration rate, which is related to a higher pyruvate dehydrogenase complex activity as compared with young adult males. This sex difference did not depend on phases of the estrous cycle, was suppressed by ovariectomy but not by orchidectomy, and no longer existed in aged mice. Concomitant analysis of brain steroids showed that pregnenolone and PROG brain levels were higher in females during the reproductive period than in males and decreased with aging in females. These findings suggest that the major male/female differences in brain pregnenolone and PROG levels may contribute to the sex differences observed in brain mitochondrial function.

    Sexual Dimorphism in the Expression of Mitochondria-Related Genes in Rat Heart at Different Ages (2015)

    Gene Ontology analysis revealed the influence of sex on various biological pathways related to cardiac energy metabolism at different ages.

    The expression of genes involved in fatty acid metabolism was significantly different between the sexes in young and adult rat hearts. (Note: In heart, fatty acids serve as a prime source of energy.)
    Adult male rats also showed higher expression of genes associated with the pyruvate dehydrogenase complex compared to females.

    In young and adult hearts, sexual dimorphism was not noted in genes encoding oxidative phosphorylation.

    In old rats, however, a majority of genes involved in oxidative phosphorylation had higher expression in females compared to males.

    Such basal differences between the sexes in cardiac expression of genes associated with energy metabolism may indicate a likely involvement of mitochondria in susceptibility to CVDs.

    In addition, female rats showed lower expression levels of apoptotic genes in hearts compared to males at all ages, which may have implications for better preservation of cardiac mass in females than in males.

    Sex-based differences in young (8-week) rats

    Fatty acid (FA) metabolism. Out of 53 genes interrogated for this category, 32 genes (60%) had higher expression levels in female rat hearts compared to males, but the effect was significant for only eight genes.
    Of these eight genes, expression of Acaa2 (acetyl-CoA acyltransferase 2), Acads (acyl-CoA dehydrogenase, C-2 to C-3 short chain), Ech1 (enoyl CoA hydratase 1, peroxisomal), Hadhb (hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), beta subunit), Hmgcs2 (3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial)), Mlycd (malonyl-CoA decarboxylase), and Pcca (propionyl CoA carboxylase, alpha polypeptide) was higher in females compared to males, and only Acsl4 (acyl-CoA synthetase long-chain family member 4) had significantly higher expression in males compared to females.

    Sex-based differences in adult (21-week) rats
    Fatty acid (FA) metabolism. GO analysis showed a significant (p = 0.001) sex effect on FA metabolism. Thirty-three of 53 genes (62%) were more highly expressed in male rat hearts compared to females, and the expression of 8 genes was significantly different between the sexes. Expression of Acaa2 (acetyl-CoA acyltransferase 2), Acadm (acyl-CoA dehydrogenase, C-4 to C-12 straight chain), Acat1 (acetyl-CoA acetyltransferase 1), Acsl6 (acyl-CoA synthetase long-chain family member 6), Cyp11a1 (cytochrome P450, family 11, subfamily a, polypeptide 1), and Oxsm (3-oxoacyl-ACP synthase, mitochondrial) was significantly higher in male compared to female hearts, whereas expression of Acot2 (acyl-CoA thioesterase 2) and Acsl3 (acyl-CoA synthetase long-chain family member 3) was significantly higher in female compared to male hearts.
    Differences in expression levels of these genes ranged from 1.11 to 1.74-fold between the sexes.

    Pyruvate dehydrogenase (PDH) complex
    GO ontology analysis showed a significant sex effect (p = 0.002) on the PDH complex in adult rats (
    Table 1). The increased expression of Pdk4 (pyruvate dehydrogenase kinase, isozyme 4) in females was confirmed by qRT-PCR (Table 2).
    etc, etc!
    Sex-dependent mental illnesses and mitochondria.(review 2017)

    The prevalence of some mental illnesses, including major depression, anxiety-, trauma-, and stress-related disorders, some substance use disorders, and later onset of schizophrenia, is higher in women than men. While the higher prevalence in women could simply be explained by socioeconomic determinants, such as income, social status, or cultural background, extensive studies show sex differences in biological, pharmacokinetic, and pharmacological factors contribute to females' vulnerability to these mental illnesses. In this review, we focus on estrogens, chronic stress, and neurotoxicity from behavioral, pharmacological, biological, and molecular perspectives to delineate the sex differences in these mental illnesses. Particularly, we investigate a possible role of mitochondrial function, including biosynthesis, bioenergetics, and signaling, on mediating the sex differences in psychiatric disorders.

    Gender differences in white matter pathology and mitochondrial dysfunction in Alzheimer’s disease with cerebrovascular disease (2016)

    Dementia risk in women is higher than in men, but the molecular neuropathology of this gender difference remains poorly defined. In this study, we used unbiased, discovery-driven quantitative proteomics to assess the molecular basis of gender influences on risk of Alzheimer’s disease with cerebrovascular disease (AD + CVD).


    We detected modulation of several redox proteins in the temporal lobe of AD + CVD subjects, and we observed sex-specific alterations in the white matter (WM) and mitochondria proteomes of female patients. Functional proteomic analysis of AD + CVD brain tissues revealed increased citrullination of arginine and deamidation of glutamine residues of myelin basic protein (MBP) in female which impaired degradation of degenerated MBP and resulted in accumulation of non-functional MBP in WM. Female patients also displayed down-regulation of ATP sub-units and cytochromes, suggesting increased severity of mitochondria impairment in women.


    Our study demonstrates that gender-linked modulation of white matter and mitochondria proteomes influences neuropathology of the temporal lobe in AD + CVD.

    Mitochondria: a central target for sex differences in pathologies. (2017)

    It is increasingly acknowledged that a sex and gender specificity affects the occurrence, development, and consequence of a plethora of pathologies. Mitochondria are considered as the powerhouse of the cell because they produce the majority of energy-rich phosphate bonds in the form of adenosine tri-phosphate (ATP) but they also participate in many other functions like steroid hormone synthesis, reactive oxygen species (ROS) production, ionic regulation, and cell death.
    Adequate cellular energy supply and survival depend on mitochondrial life cycle, a process involving mitochondrial biogenesis, dynamics, and quality control via mitophagy.
    It appears that mitochondria are the place of marked sexual dimorphism involving mainly oxidative capacities, calcium handling, and resistance to oxidative stress.
    In turn, sex hormones regulate mitochondrial function and biogenesis. Mutations in genes encoding mitochondrial proteins are the origin of serious mitochondrial genetic diseases. Mitochondrial dysfunction is also an important parameter for a large panel of pathologies including neuromuscular disorders, encephalopathies, cardiovascular diseases (CVDs), metabolic disorders, neuropathies, renal dysfunction etc. Many of these pathologies present sex/gender specificity. Here we review the sexual dimorphism of mitochondria from different tissues and how this dimorphism takes part in the sex specificity of important pathologies mainly CVDs and neurological disorders.

    Last edited: Nov 10, 2017

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