Peroxisomal hydrogen peroxide signaling: A new chapter in intracellular communication research

Hydrogen peroxide (H₂O₂), a natural metabolite commonly found in aerobic organisms, plays a crucial role in numerous cellular signaling processes. One of the key organelles involved in the cell's metabolism of H₂O₂ is the peroxisome. In this review, we first provide a concise overview of the current understanding of H₂O₂ as a molecular messenger in thiol redox signaling, along with the role of peroxisomes as guardians and modulators of cellular H₂O₂ balance. Next, we direct our focus toward the recently identified primary protein targets of H₂O₂ originating from peroxisomes, emphasizing their importance in unraveling the complex interplay between peroxisomal H₂O₂ and cell signaling. We specifically focus on three areas: signaling through peroxiredoxin redox relay complexes, calcium signaling, and phospho-signaling. Finally, we highlight key research directions that warrant further investigation to enhance our comprehension of the molecular and biochemical mechanisms linking alterations in peroxisomal H₂O₂ metabolism with disease.