Biochemistry, Genetics and Molecular Biology, Cancer Research
2
Scopus Publications
Scopus Publications
Disulfide-mediated tetramerization of TRAP1 fosters its antioxidant and pro-neoplastic activities Fiorella Faienza, Claudio Laquatra, Matteo Castelli, Gianmarco Matrullo, Salvatore Rizza, Federica Guarra, Azam Roshani Dashtmian, Alessia Magro, Paola Giglio, Chiara Pecorari, Lavinia Ferrone, Elisabetta Moroni, Francesca Pacello, Andrea Battistoni, Giorgio Colombo, Andrea Rasola, Giuseppe Filomeni Redox Biology, 2025 The mitochondrial chaperone TRAP1 exerts protective functions under diverse stress conditions. It induces metabolic rewiring and safeguards cancer cells from oxidative insults, thereby contributing to neoplastic progression. TRAP1 works as a homodimer, but recent evidence indicated that it forms tetramers whose effects remain elusive. Here, we find that TRAP1 generates redox-sensitive tetramers via disulfide bonds involving cysteines 261 and 573. TRAP1 tetramerization is elicited by oxidative stress and abrogated upon expression of the double C261S/C573R mutant. In cancer cells, the TRAP1 C261S/C573R mutant is unable to inhibit the activity of its client succinate dehydrogenase and to confer protection against oxidative insults, thus hampering the invasiveness of aggressive sarcoma cells. Overall, our findings indicate that TRAP1 undergoes tetramerization in response to oxidative stress and identify C261 and C573 as critical for TRAP1 structural rearrangement and functions.
Redox regulation of focal adhesions Gianmarco Matrullo, Giuseppe Filomeni, Salvatore Rizza Redox Biology, 2025 Focal adhesions (FAs), multi-protein complexes that link the extracellular matrix to the intracellular cytoskeleton, are key mediators of cell adhesion, migration, and proliferation. These dynamic structures act as mechanical sensors, transmitting stimuli from the extracellular to intracellular environment activating in this way signaling pathways and enabling cells to adapt to environmental changes. As such, FAs are critical for tissue organization and serve as hubs governing cell spatial arrangement within the organism. The assembly, reactivity, and functional regulation of FAs are tightly controlled by post-translational modifications, including redox modulation by reactive oxygen and nitrogen species. Increasing evidence suggests that redox signaling plays a pivotal role in both the physiological and pathological functions of FAs and their downstream processes. Redox regulation affects various components of the FA complex, including integrins, focal adhesion kinase 1 (FAK1), SRC, adapter proteins, and cytoskeletal elements. In this review, we provide an updated overview of the complex interplay between redox signaling and post-translational modifications in FAs. We explore how redox reactions influence the structure, dynamics, and function of FAs, shedding light on their broader implications in health and disease.
