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FIGURE 1
Evaluation of zag in multiple zebrafish models of mitochondrial dysfunction. Zag is a small-molecule sGC stimulator (structure at top) that increases NO-sGC-cGMP signaling. Here, we tested zag in multiple larval and adult zebrafish genetic and/or pharmacologic models of mitochondrial disease (center). Toxicity was evaluated in larval fish, and accumulation analysis (BioAnalysis) was performed on adult zebrafish brain and tail muscle. The larval models were evaluated for cell death, as evidenced by the presence of a gray brain and neuromuscular activity (lower left and upper right), swimming activity (lower right), and classical biochemical markers (middle left). The adult models were evaluated in swim activity assays (middle right, Loligo swim tunnels) while measuring oxygen consumption during a defined exercise protocol.