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Background: Muscle atrophy is a common consequence of the loss of innervation and is accompanied by mitochondrial dysfunction. Mitophagy is the adaptive process through which damaged mitochondria are removed via the lysosomes, which are regulated in part by the transcription factor TFE3. The role of lysosomes and TFE3 are poorly understood in muscle atrophy, and the effect of biological sex is widely underreported. Methods: Wild-type (WT) mice, along with mice lacking TFE3 (KO), a transcriptional regulator of lysosomal and autophagy-related genes, were subjected to unilateral sciatic nerve denervation for up to 7 days, while the contralateral limb was sham-operated and served as an internal control. A subset of animals was treated with colchicine to capture mitophagy flux. Results: WT females exhibited elevated oxygen consumption rates during active respiratory states compared to males, however this was blunted in the absence of TFE3. Females exhibited higher mitophagy flux rates and greater lysosomal content basally compared to males that was independent of TFE3 expression. Following denervation, female mice exhibited less muscle atrophy compared to male counterparts. Intriguingly, this sex-dependent muscle sparing was lost in the absence of TFE3. Denervation resulted in 45% and 27% losses of mitochondrial content in WT and KO males respectively, however females were completely protected against this decline. Decreases in mitochondrial function were more severe in WT females compared to males following denervation, as ROS emission was 2.4-fold higher. In response to denervation, LC3-II mitophagy flux was reduced by 44% in females, likely contributing to the maintenance of mitochondrial content and elevated ROS emission, however this response was dysregulated in the absence of TFE3. While both males and females exhibited increased lysosomal content following denervation, this response was augmented in females in a TFE3-dependent manner. Conclusions: Females have higher lysosomal content and mitophagy flux basally compared to males, likely contributing to the improved mitochondrial phenotype. Denervation-induced mitochondrial adaptations were sexually dimorphic, as females preferentially preserve content at the expense of function, while males display a tendency to maintain mitochondrial function. Our data illustrate that TFE3 is vital for the sex-dependent differences in mitochondrial function, and in determining the denervation-induced atrophy phenotype. [ABSTRACT FROM AUTHOR]

Dissolved helium atoms evaporate from liquids in super-Maxwellian speed distributions because their interactions are too weak to enforce full thermal equilibration at the surface as they are “squeezed” out of solution. The excess speeds of these He atoms reflect their final interactions with solvent and solute molecules at the surfaces of water and other liquids. We extend this observation by monitoring He atom evaporation from salty water solutions coated with surfactants. These surface-active molecules span neutral, anionic, and cationic amphiphiles: butanol, 3-methyl-1-butanol, pentanol, pentanoic acid, pentanoate, tetrabutylammonium, benzyltrimethylammonium, hexyltrimethylammonium, and dodecyltrimethylammonium, each characterized by surface tension measurements. The helium energy distributions, recorded in vacuum using a salty water microjet, reveal a sharp distinction between neutral and ionic surfactant films. Helium atoms evaporate through neutral surfactant monolayers in speed distributions that are similar to a pure hydrocarbon, reflecting the common alkyl chains of both. In contrast, He atoms appear to evaporate through ionic surfactant layers in distributions that are closer to pure salty water. We speculate that the ionic surfactants distribute themselves more loosely and deeply through the top layers of the aqueous solution than do neutral surfactants, with gaps between the surfactants that may be filled with salty water. This difference is supported by prior molecular dynamics simulations and ion scattering measurements of surfactant solutions. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of the study?Do interindividual differences in trainability exist for morphological and molecular skeletal muscle responses to aerobic exercise training?What is the main finding and its importance?Interindividual differences in trainability were present for some, but not all, morphological and molecular outcomes included in our study.Our findings suggest that it is inappropriate, and perhaps erroneous, to assume that variability in observed responses reflects interindividual differences in trainability in skeletal muscle responses to aerobic exercise training. Studies have interpreted a wide range of morphological and molecular changes in human skeletal muscle as evidence of interindividual differences in trainability. However, these interpretations fail to account for the influence of random measurement error and within‐subject variability. The purpose of the present study was to use the standard deviation of individual response (SDIR) statistic to test the hypothesis that interindividual differences in trainability are present for some but not all skeletal muscle outcomes. Twenty‐nine recreationally active males (age: 21 ± 2 years; BMI: 24 ± 3 kg/m2; V̇O2peak; 45 ± 7 ml/kg/min) completed 4 weeks of continuous training (REL; n = 14) or control (n = 15). Maximal enzyme activities (citrate synthase and β‐hydroxyacyl‐CoA dehydrogenase), capillary density, fibre type composition, fibre‐specific succinate dehydrogenase activity and substrate storage (intramuscular triglycerides and glycogen), and markers of mitophagy (BCL2‐interacting protein 3 (BNIP3), BNIP3‐like protein, parkin and PTEN‐induced kinase 1) were measured in vastus lateralis samples collected before and after the intervention. We also calculated SDIR values for V̇O2peak, peak work rate and the onset of blood lactate accumulation for the REL group and a separate group that exercised at the negative talk test stage. Although positive SDIR values – indicating interindividual differences in trainability – were obtained for aerobic capacity outcomes, maximal enzyme activities, capillary density, all fibre‐specific outcomes and BNIP3 protein content, the remaining outcomes produced negative SDIR values indicating a large degree of random measurement error and/or within‐subject variability. Our findings question the interpretation of heterogeneity in observed responses as evidence of interindividual differences in trainability and highlight the importance of including control groups when analysing individual skeletal muscle response to exercise training. [ABSTRACT FROM AUTHOR]