N-Terminal Functional Domain of Gasdermin A3 Regulates Mitochondrial Homeostasis via Mitochondrial Targeting
June 2015
in “
Journal of biomedical science
”
Gasdermin A3 Gsdma3 N-terminal domain C-terminal domain mitochondrial targeting oxidative stress Hsp90 Tom70 Trap1 mitochondrial reactive oxygen species ROS mitochondrial membrane potential mitochondrial permeability transition skin inflammation hair loss keratinocyte differentiation cell death signals mitochondrial ROS mitochondrial permeability cell death
TLDR Mutations in Gasdermin A3 cause skin inflammation and hair loss by disrupting mitochondria.
The study revealed that mutations in the C-terminal domain of Gasdermin A3 (Gsdma3) unmasked its N-terminal domain, leading to mitochondrial targeting and increased oxidative stress. This process involved the N-terminal domain associating with Hsp90 and being transported to mitochondria via Tom70, where it interacted with Trap1, resulting in elevated mitochondrial reactive oxygen species (ROS), loss of mitochondrial membrane potential, and mitochondrial permeability transition. These findings suggested that Gsdma3 mutations are gain-of-function, causing skin inflammation and hair loss by disrupting mitochondrial homeostasis. The study proposed that Gsdma3 modulates keratinocyte responses to differentiation and cell death signals through its impact on mitochondria.
