Impact of mitochondrial reductive stress due to respiratory chain limitation on cancer via posttranslational modifications

/NAD(P)H balance, perturbs acyl-CoA and citric acid cycle metabolite pools, and rewires protonmotive force-linked matrix chemistry and thiol buffering. These constraints are predicted to remodel lysine acylations, HIF hydroxylation, histone and DNA methylation, cysteine-centered redox PTMs, phosphorylation networks, ubiquitin-dependent proteostasis, ADP-ribosylation, and lactylation. Together, these relationships support a site- and context-dependent PTM-routing state in which the position of respiratory chain limitation and the local tumor environment shape which PTM chemistries become rate-limiting, adaptive, or growth-restrictive.