GDF15 and mitochondrial disease: Indeed, mitochondrial disease patients had higher circulatory GDF15 levels compared to non-mitochondrial neuromuscular disease controls (63, 64, 68–71). Further, several studies utilized mitochondrial dysfunction to induce a neurodegenerative phenotype in vitro and in vivo, which caused elevated GDF15 expression and secretion (28, 36, 39, 57–59). Therefore, heightened circulatory GDF15 indicates mitochondrial stress and dysfunction, likely associated with neurodegenerative pathophysiology.