A fuller understanding of the involvement of mitochondria in cases of infertility linked to ovarian ageing would contribute to a better management of the disorder in the future.

No abstract

We compared the metabolomic profile of aqueous humor from patients with primary open-angle glaucoma (POAG; n = 26) with that of a group of age-and sex-matched non-POAG controls (n = 26), all participants undergoing cataract surgery. Supervised paired partial leastsquares discriminant analysis showed good predictive performance for test sets with a median area under the receiver operating characteristic of 0.89 and a p-value of 0.0087. Twenty-three metabolites allowed discrimination between the two groups. Univariate analysis after the Benjamini−Hochberg correction showed significant differences for 13 of these metabolites. The POAG metabolomic signature indicated reduced concentrations of taurine and spermine and increased concentrations of creatinine, carnitine, three short-chain acylcarnitines, 7 amino acids (glutamine, glycine, alanine, leucine, isoleucine, hydroxyl-proline, and acetyl-ornithine), 7 phosphatidylcholines, one lysophosphatidylcholine, and one sphingomyelin. This suggests an alteration of metabolites involved in osmoprotection (taurine and creatinine), neuroprotection (spermine, taurine, and carnitine), amino acid metabolism (7 amino acids and three acylcarnitines), and the remodeling of cell membranes drained by the aqueous humor (hydroxyproline and phospholipids). Five of these metabolic alterations, already reported in POAG plasma, concern spermine, C3 and C4 acylcarnitines, PC aa 34:2, and PC aa 36:4, thus highlighting their importance in the pathogenesis of glaucoma.

Our results highlight a systemic and age-related mitochondrial defect in the pathogenesis of POAG.

No abstract

PURPOSE. To investigate the plasma concentration of nicotinamide in primary open-angle glaucoma (POAG). METHODS. Plasma of 34 POAG individuals was compared to that of 30 age-and sex-matched controls using a semiquantitative method based on liquid chromatography coupled to highresolution mass spectrometry. Subsequently, an independent quantitative method, based on liquid chromatography coupled to mass spectrometry, was used to assess nicotinamide concentration in the plasma from the same initial cohort and from a replicative cohort of 20 POAG individuals and 15 controls. RESULTS. Using the semiquantitative method, the plasma nicotinamide concentration was significantly lower in the initial cohort of POAG individuals compared to controls and further confirmed in the same cohort, using the targeted quantitative method, with mean concentrations of 0.14 lM (median: 0.12 lM; range, 0.06-0.28 lM) in the POAG group (À30%; P ¼ 0.022) and 0.19 lM (median: 0.18 lM; range, 0.08-0.47 lM) in the control group. The quantitative dosage also disclosed a significantly lower plasma nicotinamide concentration (À33%; P ¼ 0.011) in the replicative cohort with mean concentrations of 0.14 lM (median: 0.14 lM; range, 0.09-0.25 lM) in the POAG group, and 0.19 lM (median: 0.21 lM; range, 0.09-0.26 lM) in the control group. CONCLUSIONS. Glaucoma is associated with lower plasmatic nicotinamide levels, compared to controls, suggesting that nicotinamide supplementation might become a future therapeutic strategy. Further studies are needed, in larger cohorts, to confirm these preliminary findings.

No abstract

Mitochondrial dynamics and distribution are critical for supplying ATP in response to energy demand. CLUH is a protein involved in mitochondrial distribution whose dysfunction leads to mitochondrial clustering, the metabolic consequences of which remain unknown. To gain insight into the role of CLUH on mitochondrial energy production and cellular metabolism, we have generated CLUHknockout cells using CRISPR/Cas9. Mitochondrial clustering was associated with a smaller cell size and with decreased abundance of respiratory complexes, resulting in oxidative phosphorylation (OXPHOS) defects. This energetic impairment was found to be due to the alteration of mitochondrial translation and to a metabolic shift towards glucose dependency. Metabolomic profiling by mass spectroscopy revealed an increase in the concentration of some amino acids, indicating a dysfunctional Krebs cycle, and increased palmitoylcarnitine concentration, indicating an alteration of fatty acid oxidation, and a dramatic decrease in the concentrations of phosphatidylcholine and sphingomyeline, consistent with the decreased cell size. Taken together, our study establishes a clear function for CLUH in coupling mitochondrial distribution to the control of cell energetic and metabolic status.