Faculty mentor/PI email address
santhanam@rowan.edu
Keywords
Magnesium induced signaling, PYGM knockout, McArdle disease
Date of Presentation
5-6-2026 12:00 AM
Poster Abstract
McArdle disease, caused by mutations in the PYGM gene, impairs glycogenolysis in skeletal muscle, reducing lactate production and leading to energy deficits, fatigue, and risk of rhabdomyolysis. Using a CRISPR/Cas9-generated PYGM knockout (KO) rat model, we investigated whether reduced lactate production disrupts mitochondrial magnesium (Mg²⁺) homeostasis. KO rats failed to elevate lactate during static muscle contraction and showed diminished mitochondrial Mg²⁺ uptake, disrupted ATP synthesis, and impaired mitochondrial respiration. In vitro, caffeine-stimulated KO myotubes lacked lactate production and mitochondrial Mg²⁺ uptake despite preserved Ca²⁺ oscillations. Raising glucose concentration restored lactate levels, rescued mitochondrial Mg²⁺ transport, and improved metabolic output in KO cells. These findings identify lactate as a key regulator of mitochondrial Mg²⁺ homeostasis and reveal a novel lactate–Mg²⁺–ATP axis linking glycogenolysis to mitochondrial energy balance in McArdle disease.
Disciplines
Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Medicine and Health Sciences
Lactate-Induced Mitochondrial Magnesium Uptake and Its Metabolic Implications in the McArdle’s Disease Model
McArdle disease, caused by mutations in the PYGM gene, impairs glycogenolysis in skeletal muscle, reducing lactate production and leading to energy deficits, fatigue, and risk of rhabdomyolysis. Using a CRISPR/Cas9-generated PYGM knockout (KO) rat model, we investigated whether reduced lactate production disrupts mitochondrial magnesium (Mg²⁺) homeostasis. KO rats failed to elevate lactate during static muscle contraction and showed diminished mitochondrial Mg²⁺ uptake, disrupted ATP synthesis, and impaired mitochondrial respiration. In vitro, caffeine-stimulated KO myotubes lacked lactate production and mitochondrial Mg²⁺ uptake despite preserved Ca²⁺ oscillations. Raising glucose concentration restored lactate levels, rescued mitochondrial Mg²⁺ transport, and improved metabolic output in KO cells. These findings identify lactate as a key regulator of mitochondrial Mg²⁺ homeostasis and reveal a novel lactate–Mg²⁺–ATP axis linking glycogenolysis to mitochondrial energy balance in McArdle disease.