-Lipoic acid (LA) is widely included in mitochondrial cocktails recommended to patients with primary mitochondrial disorders, yet its mechanism of action remains unclear. Here, we define the intracellular availability and functional utilization of LA in mammalian cells. We show that LA exists in two functionally distinct cellular pools: a low-abundance free pool and a protein-bound pool generated through mitochondrial fatty acid synthesis (mtFAS). Disruption of the mtFAS pathway abolishes protein lipoylation and impairs oxidative phosphorylation without altering free LA levels. Conversely, supplementation with exogenous LA markedly increases free intracellular LA without restoring protein lipoylation, mitochondrial respiration, or cell proliferation. Instead, the cellular effects of LA supplementation resemble those of the antioxidant N-acetylcysteine. These findings clarify the mechanism of action of a widely used mitochondrial supplement and identify a fundamental disconnect between cellular LA abundance and mitochondrial utilization, challenging the rationale for using LA supplementation to restore mitochondrial function.
Crisis support teams’ technological openness and learning attitudes toward the AI based virtual patient system crisis support VR
BackgroundAgainst the backdrop of escalating global humanitarian crises, innovative didactic simulations are becoming increasingly important. A promising alternative to traditional classroom-based didactics for learning psychological