Importance of mitochondrial protein import for regulating neuronal integrity

The laboratory headed by TONG Chao, a professor with the Life Sciences Institute and Innovation Center for Cell Signaling Network, published an online article entitled “Mitochondrial protein import regulates cytosolic protein homeostasis and neuronal integrity” in Autophagy on June 18, 2018.

Mitochondria are the primary site for ATP synthesis, and they are also involved in the transmission of signaling molecules and various metabolic processes. Neurodegeneration is characterized by protein aggregate deposits and mitochondrial malfunction. TONG Chao et al. discover that the reduction in Tom40 (translocase of outer membrane 40) expression leads to accumulation of ubiquitin (Ub)-positive protein aggregates engulfed by Atg8a-positive membranes. Other macroautophagy markers are also abnormally accumulated. In nerve tissues, reduction in Tom40 activity results in aggregate formation and neurodegeneration. Rather than diminishing the neurodegenerative phenotypes, overexpression of Pink1 enhances them.

These findings reveal that defects in mitochondrial protein import may be the key to linking imbalanced proteostasis and mitochondrial defects, thereby laying a theoretical foundation for the treatment of neurodegenerative disorders.