Delving into the mechanisms underlying HPDL-related disorders with a multi-model approach

This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2021

This project will investigate the function of HPDL, a new mitochondrial protein recently demonstrated to be associated with severe, neonatal-onset disease with brain imaging resembling Leigh syndrome, or milder manifestations mimicking cerebral palsy or adolescent-onset spastic paraplegia.

Recent data suggest that HPDL is involved in the biosynthesis of CoQ10 but mouse models cannot help to clarify if this potential role explains human pathologies and might forecast potential attempts to therapies.

We will try to fill these gaps with the creation of new investigation tools such as HPDL cortical neurons and organoids, and null strains in worms and fish. We will study how HPDL acts during cortical development and proposes to assess the ability of CoQ10 and its quinonic precursors to rescue HPDL in vitro and in vivo.