Loss of function variants in HPDL impair human cortical development via alterations of mitochondrial function.

ABSTRACT: Human brain development is highly regulated by several spatiotemporal processes, which disruption can result in severe neurological disorders. Emerging evidence highlights the pivotal role of mitochondrial function as one of these fundamental pathways involved in neurodevelopment. Our study investigates the role of 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) protein in cortical neurogenesis and mitochondrial activity, since mutations in the HPDL gene are associated with a childhood-onset form of hereditary spastic paraplegia characterized by corticospinal tract degeneration and cortical abnormalities. Starting from mutant neuroblastoma cells, we demonstrated that HPDL is important to respiratory chain supercomplex assembly and cellular redox balance. Moreover, RNA-seq studies revealed

SUBMITTER: Baggiani M 

PROVIDER: S-EPMC12948981 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature