The interplay between sex, time of day, fasting status, and their impact on cardiac mitochondrial structure, function, and dynamics.

Mitochondria morphology and function, and their quality control by mitophagy, are essential for heart function. We investigated whether these are influenced by time of the day (TOD), sex, and fed or fasting status, using transmission electron microscopy (EM), mitochondrial electron transport chain (ETC) activity, and mito-QC reporter mice. We observed peak mitochondrial number at ZT8 in the fed state, which was dependent on the intrinsic cardiac circadian clock, as hearts from cardiomyocyte-specific BMAL1 knockout (CBK) mice exhibit different TOD responses.

Acute inhibition of OGA sex-dependently alters the networks associated with bioenergetics, autophagy, and neurodegeneration.

The accumulation of neurotoxic proteins characteristic of age-related neurodegenerative pathologies such as Alzheimer's and Parkinson's diseases is associated with the perturbation of metabolism, bioenergetics, and mitochondrial quality control. One approach to exploit these interactions therapeutically is to target the pathways that regulate metabolism. In this respect, the nutrient-sensing hexosamine biosynthesis pathway is of particular interest since it introduces a protein post-translational modification known as O-GlcNAcylation, which modifies different proteins in control versus neurodegenerative disease postmortem brains.

High throughput measurement of metabolism in planarians reveals activation of glycolysis during regeneration.

Planarians are outstanding models for studying mechanisms of regeneration; however, there are few methods to measure changes in their metabolism. Examining metabolism in planarians is important because the regenerative process is dependent on numerous integrated metabolic pathways, which provide the energy required for tissue repair as well as the ability to synthesize the cellular building blocks needed to form new tissue. Therefore, we standardized an extracellular flux analysis method to measure mitochondrial and glycolytic activity in live planarians during normal growth as well as during regeneration.