Microarray expression data from iSOD2 adapted livers

Transient mitochondrial stress can promote beneficial physiological responses and longevity, termed "mitohormesis." To interrogate mitohormetic pathways in mammals, we generated mice in which mitochondrial superoxide dismutase 2 (SOD2) can be knocked-down in an inducible and reversible manner (iSOD2-KD). Depleting SOD2 only during embryonic development did not cause post-natal lethality, allowing us to probe adaptive responses to mitochondrial oxidant stress in adult mice. Liver from adapted mice had increased mitochondrial biogenesis and antioxidant gene expression and fewer reactive oxygen species. Gene expression analysis implicated non- canonical activation of the Nrf2 antioxidant and PPAR-PGC-1 mitochondrial signaling pathways in this response. Transient SOD2 knock-down in embryonic fibroblasts from iSOD2-KD mice also resulted in adaptive mitochondrial changes, enhanced antioxidant capacity, and resistance to a subsequent oxidant challenge. We propose that mitohormesis in response to mitochondrial oxidative stress in mice involves sustained basal activation of mitochondrial and antioxidant signaling pathways to establish a heightened antioxidant state. We used microarrays to determine differentially expressed genes in mouse liver after transient SOD2 knock-down during mouse embryogenesis. SOD2 was knocked down during days 0-12.5e in utero. At four weeks of age, animals were sacrificed and microarray analysis was conducted on mouse liver. Three iSOD2 adapted liver samples from shRNA 1 and three samples from shRNA 2 were analyzed. Four total rtTA only littermate controls were analyzed, including 3 from the shRNA 2 cohort and 1 from the shRNA 1 cohort. Approximately 1 mg of RNA was sent to the Yale Center for Genome Analysis for microarray analysis on Affymetrix Mouse 2.0st array plates.