Research project

MFAG, Rif. 20316- The F-ATP synthase inhibitor IF1 binds to a novel site and promotes tumorigenesis: displacement as anticancer strategy . (DSB.AD001.109)

Thematic area

Biomedical sciences

Project area

Oncologia e Immunologia (DSB.AD001)

Structure responsible for the research project

Institute of neuroscience (IN)

Project manager

Phone number: 049 8276361


F-ATP synthase is a large multisubunit complex located in the inner mitochondrial membrane. We have recently discovered that
this enzyme, which synthesizes ATP in energized mitochondria, under conditions of oxidative stress and Ca2+ overload forms
the Permeability Transition Pore (PTP), a channel whose opening can cause cell death. The inhibitor protein IF1 binds to, and
blocks F-ATP synthase during ATP hydrolysis. Interestingly, IF1 has been associated to tumorigenic growth as it is
overexpressed in glioma, colon, lung and breast cancers. Evidence exists to suggest that IF1 causes a shift to Warburg
metabolism during neoplastic growth by inhibiting ATP synthesis, a finding that would imply the existence of a second, hitherto
unidentified binding site on F-ATP synthase. The most plausible candidate is the OSCP subunit, a key modulator site of the PTP
that was shown to interact with the C- terminus of IF1 in vitro. Whether IF1 binding to F-ATP synthase modulates the PTP has
never been addressed.


We hope to identify (i) a novel IF1 binding site on F-ATP synthase which is involved in cancer growth through its PTP
inhibitory effect; (ii) new targeted molecules, able to displace IF1 from its binding site, that are effective in preventing
tumorigenic growth; (iii) drugs effective in vivo in counteracting neoplastic formations.

Start date of activity



Mitochondria, Apoptosis, Biochemistry

Last update: 04/12/2023