By contrast, under stress conditions, such as AKI or in tubular cells stressed by inflammatory cytokines (e.g. TWEAK), the decrease in SIRT3 expression, and, potentially, in SIRT3 decrotonylase activity, might lead to increased histone crotonylation, thus limiting the downregulation of protective genes such as PGC-1α (Fig. 8). The gene discussed is PPARGC1A; the disease is acute kidney injury.