Calcium Deregulation and Mitochondrial Bioenergetics in GDAP1-Related CMT Disease

• Main Authors: Paloma González-Sánchez, Jorgina Satrústegui, Francesc Palau, Araceli del Arco
• Format: Article
• Language: English
• Published: MDPI AG 2019-01-01
• Series: International Journal of Molecular Sciences
• Subjects: GDAP1; recessive mutations; store operated calcium entry; mitochondrial location; calcium regulated cell respiration
• Online Access: http://www.mdpi.com/1422-0067/20/2/403

The pathology of Charcot-Marie-Tooth (CMT), a disease arising from mutations in different genes, has been associated with an impairment of mitochondrial dynamics and axonal biology of mitochondria. Mutations in ganglioside-induced differentiation-associated protein 1 (GDAP1) cause several forms of CMT neuropathy, but the pathogenic mechanisms involved remain unclear. GDAP1 is an outer mitochondrial membrane protein highly expressed in neurons. It has been proposed to play a role in different aspects of mitochondrial physiology, including mitochondrial dynamics, oxidative stress processes, and mitochondrial transport along the axons. Disruption of the mitochondrial network in a neuroblastoma model of GDAP1-related CMT has been shown to decrease Ca2+ entry through the store-operated calcium entry (SOCE), which caused a failure in stimulation of mitochondrial respiration. In this review, we summarize the different functions proposed for GDAP1 and focus on the consequences for Ca2+ homeostasis and mitochondrial energy production linked to CMT disease caused by different GDAP1 mutations.