Role of Sex Hormones on Brain Mitochondrial Function, with Special Reference to Aging and Neurodegenerative Diseases

Gaignard, Pauline; Lière, Philippe; Thérond, Patrice; Schumacher, Michaël; Slama, Abdelhamid; Guennoun, Rachida

doi:10.3389/fnagi.2017.00406

Cited by 98 publications

(65 citation statements)

References 162 publications

(232 reference statements)

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“…The mice were housed in groups of four in individually ventilated cages with free access to chow and water. Mitochondrial function is affected by sex steroids and the sAC inhibitor 2‐hydroxy estradiol is an estrogen derivative (Gaignard et al, ; Steegborn, Litvin, Hess, et al, ). Thus, in order to avoid any potential effects of hormones from female mice being in different stages of the estrous cycle, all experiments were performed in male mice, and hence sex‐specific aspects of the work could not be evaluated.…”

Section: Methodsmentioning

confidence: 99%

Soluble adenylyl cyclase‐mediated cAMP signaling and the putative role of PKA and EPAC in cerebral mitochondrial function

Jakobsen

Lange

Bak

2019

J of Neuroscience Research

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Mitochondria produce the bulk of the ATP in most cells, including brain cells. Regulating this complex machinery to match the energetic needs of the cell is a complicated process that we have yet to understand in its entirety. In this context, 3′,5′‐cyclic AMP (cAMP) has been suggested to play a seminal role in signaling‐metabolism coupling and regulation of mitochondrial ATP production. In cells, cAMP signals may affect mitochondria from the cytosolic side but more recently, a cAMP signal produced within the matrix of mitochondria by soluble adenylyl cyclase (sAC) has been suggested to regulate respiration and thus ATP production. However, little is known about these processes in brain mitochondria, and the effectors of the cAMP signal generated within the matrix are not completely clear since both protein kinase A (PKA) and exchange protein activated by cAMP 1 (EPAC1) have been suggested to be involved. Here, we review the current knowledge and relate it to brain mitochondria. Further, based on measurements of respiration, membrane potential, and ATP production in isolated mouse brain cortical mitochondria we show that inhibitors of sAC, PKA, or EPAC affect mitochondrial function in distinct ways. In conclusion, we suggest that brain mitochondria do regulate their function via sAC‐mediated cAMP signals and that both PKA and EPAC could be involved downstream of sAC. Finally, due to the role of faulty mitochondrial function in a range of neurological diseases, we expect that the function of sAC‐cAMP‐PKA/EPAC signaling in brain mitochondria will likely attract further attention.

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Section: Methodsmentioning

confidence: 99%

Soluble adenylyl cyclase‐mediated cAMP signaling and the putative role of PKA and EPAC in cerebral mitochondrial function

Jakobsen

Lange

Bak

2019

J of Neuroscience Research

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“…Indeed, even if all mitochondria and the mtDNA are uniquely inherited from the mother (Giles et al, 1980), differences in protein composition and function are acquired during development and as a result, multiple facets of mitochondrial biology differ by sex in adult animals (Ventura-Clapier et al, 2017). This is, in part, due to the fact that sex hormones regulate mitochondrial function and biogenesis (Gaignard et al, 2017). Metabolomic signatures also, which indirectly reflect mitochondrial and cellular metabolism of the whole organism, show that up to one-third of metabolites at baseline differ between women and men (Krumsiek et al, 2015).…”

Section: Sexual Dimorphism In Mitochondria and Stress Physiologymentioning

confidence: 99%

An energetic view of stress: Focus on mitochondria

Picard

McEwen

Epel

et al. 2018

Frontiers in Neuroendocrinology

386

309

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Energy is required to sustain life and enable stress adaptation. At the cellular level, energy is largely derived from mitochondria – unique multifunctional organelles with their own genome. Four main elements connect mitochondria to stress: (1) Energy is required at the molecular, (epi)genetic, cellular, organellar, and systemic levels to sustain components of stress responses; (2) Glucocorticoids and other steroid hormones are produced and metabolized by mitochondria; (3) Reciprocally, mitochondria respond to neuroendocrine and metabolic stress mediators; and (4) Experimentally manipulating mitochondrial functions alters physiological and behavioral responses to psychological stress. Thus, mitochondria are endocrine organelles that provide both the energy and signals that enable and direct stress adaptation. Neural circuits regulating social behavior – as well as psychopathological processes – are also influenced by mitochondrial energetics. An integrative view of stress as an energy-driven process opens new opportunities to study mechanisms of adaptation and regulation across the lifespan.

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“…These findings indicate that oxidative stress is strongly related to activation of the extrinsic (death receptor) apoptotic pathway. Oxidative stress involves the excessive generation of ROS and damage to the mitochondria, which are the site of ROS generation and the target of oxidative stress‐induced damage . Our study shows that the generation of ROS was significantly increased in regular L‐929 cells treated with fluoride; however, the generation of ROS was not increased in FR L‐929 cells exposed to the same treatment conditions.…”

Section: Discussionmentioning

confidence: 57%

“…The extrinsic pathway is activated by the interaction of the transmembrane death receptors TNF‐α or Fas with their ligands, which eventually leads to the activation of caspase‐3 . In addition, oxidative stress causes damage to cellular components, especially the mitochondria, which are the site of ROS generation and also the target of oxidative stress‐induced damage .…”

mentioning

confidence: 99%

Fluoride resistance in fibroblasts is conferred via reduced susceptibility to oxidative stress and apoptosis

Zhong

et al. 2020

FEBS Open Bio

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Chronic fluoride exposure from drinking water may result in endemic fluorosis. To better understand the mechanisms by which some people are resistant to fluorosis, here we investigated the effect of treatment with NaF (sodium fluoride) on production of reactive oxygen species (ROS), morphological changes in mitochondria, the mRNA expression of Fas ligand (Fas‐L), and the protein expression of cleaved caspase‐3 in regular L‐929 cells and fluoride‐resistant (FR) L‐929 cells. While morphological changes indicative of apoptosis and a network of fragmented mitochondria were observed in regular L‐929 cells after NaF treatment, there were no morphological changes in FR L‐929 cells after NaF treatment. Treatment with 10 mm NaF induced a significant difference in the production of ROS, triggered the expression of cleaved caspase‐3, and upregulated the mRNA expression of Fas‐L in regular L‐929 cells. However, there was no significant production of ROS in FR L‐929 cells. Additionally, cleaved caspase‐3 and upregulated Fas‐L were not detected in FR L‐929 cells. These results suggest that FR fibroblasts are resistant to oxidative stress and apoptosis induced by fluoride.

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Role of Sex Hormones on Brain Mitochondrial Function, with Special Reference to Aging and Neurodegenerative Diseases

Cited by 98 publications

References 162 publications

Soluble adenylyl cyclase‐mediated cAMP signaling and the putative role of PKA and EPAC in cerebral mitochondrial function

Soluble adenylyl cyclase‐mediated cAMP signaling and the putative role of PKA and EPAC in cerebral mitochondrial function

An energetic view of stress: Focus on mitochondria

Fluoride resistance in fibroblasts is conferred via reduced susceptibility to oxidative stress and apoptosis

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