Investigating the Time-Dependent Effects of Sulforaphane, Urolithin A, and ZLN005 as Inducers of Mitochondrial Turnover in Muscle

The mitochondrial profile of skeletal muscle is a strong determinant of whole-body metabolic health. The overarching mechanisms that contribute to organelle maintenance and optimal function involve their production, preservation, and recycling. Impairments in the vast connections between these mechanisms have been reported to develop because of poor signal transduction, thus leading to complications in mitochondrial content and function, resulting in a catabolic phenotype. While the importance of these mechanisms is uncontested, their characterization continues to unfold. We pursued three agents, Sulforaphane, Urolithin A, and ZLN005, which have been partially recognized in their ability to induce the Nrf-2/ARE antioxidant system, mitophagy, or mitochondrial biogenesis, respectively. As a novel approach, we sought to add to their characterization by examining the time-dependent effects on mitochondrial refreshment using an in vitro model of skeletal muscle following treatment. Our data indicate the potential of these agents, either alone or in combination, to improve mitochondrial homeostasis in muscle.