HTLV-1 Tax induces PINK1-Parkin-dependent mitophagy to mitigate activation of the cGAS-STING pathway.

ABSTRACT: Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATLL) and the neuroinflammatory disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 Tax regulatory protein plays a critical role in HTLV-1 persistence and pathogenesis; however, the underlying mechanisms are poorly understood. Here we show that Tax dynamically regulates mitochondrial reactive oxygen species (ROS) and membrane potential to trigger mitochondrial dysfunction. Tax is recruited to damaged mitochondria through its interaction with the IKK regulatory subunit NEMO and directly engages the ubiquitin-dependent PINK1-Parkin pathway to induce mitophagy. Tax also recruits autophagy receptors NDP52 and p62/SQSTM1 to damaged mitochondria to induce mit

SUBMITTER: Mohanty S 

PROVIDER: S-EPMC11952555 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature