BtBs seminar - From DNA Damage to Bioenergetic Collapse: Genome–Mitochondria Crosstalk in ALS

Silvia Barabino, Department of Biotechnology and Biosciences, University of Milano-Bicocca

Amyotrophic lateral sclerosis (ALS) is characterized by both genomic instability and mitochondrial dysfunction, yet the mechanistic connection between these hallmarks remains unclear. We previously demonstrated that the RNA-binding protein FUS promotes DNA damage response (DDR) signaling through liquid-liquid phase separation, enabling the recruitment of repair factors and proper DNA repair organization. Now we found that persistent DDR signaling is sufficient to trigger an early bioenergetic collapse characterized by reduced respiration and ATP production. Now we identify a potential mechanistic pathway linking DDR-induced PARP1 activation and NAD+ depletion to impaired oxidative phosphorylation. Importantly, these defects are reversible through DNA damage resolution, PARP1 inhibition, or NAD+ replenishment. Our findings identify a pathogenic nuclear–mitochondrial axis linking genomic instability to metabolic dysfunction in ALS and suggest new therapeutic opportunities targeting DDR-driven bioenergetic failure.

The seminar is OPEN to all.

ONLINE REGISTRATION for the seminar is a mandatory requirement for those who wish to request the CERTIFICATE OF ATTENDANCE, which, together with the signature on the ATTENDANCE SHEET, will confirm actual participation.

The seminar's online registration will be available a few days before the event.

for information:  infobtbs@unimib.it

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