We demonstrate that PINK1 sequesters the master regulator HNF4alpha, hampering DNA repair.
Blocking mitophagy reduce survival of persister cells; patients whose cancer cells show signatures of increased mitophagy present a shorter survival.

Among the few pathways upregulated in persister cells, there was #mitophagy. Indeed mitochondrial turnover and neo-synthesis was strongly activated in persister cells, driven by PINK1.

Upon prolonged exposure, tolerant cells morph into a persistence status, where DNA repair is reduced. @daweonline.bsky.social using #scGETseq revealed that in persister cells chromatin became pervasively compacted with concomitant transcriptional reduction.

Blocking autophagy hampers this tolerant response increasing chemotherapy efficacy in various cancer types.

Differing from #persistency, which occurs after long-term exposure to drugs, #tolerance is triggered immediately after anticancer treatment and provides a key survival advantage to cancer cells. This response is associated with increased DNA repair, driven by enhanced autophagy.

Seeking to identify new paths exploited by #cancer cells to withstand chemotherapy, together with @nathaliebalaban and @Alon Gutfreund , we found that cancer cells from different tumour origins exploit an atavistic tolerance response that was first identified in bacteria.

Delighted to post our most recent paper in @natcomms lead by @SimonaPunzi, within the frame of an Accelerator grant funded by @CRUK and @AIRC.
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