Raising NAD ⁺ Level Stimulates Short-Chain Dehydrogenase/Reductase Proteins to Alleviate Heart Failure Independent of Mitochondrial Protein Deacetylation

Abstract

These findings identify SDR proteins as important regulators of mitochondrial function and molecular targets of NAD⁺-based therapy. Furthermore, the benefit is observed regardless of Sirt3-mediated mitochondrial protein deacetylation, a widely held mechanism for NAD⁺-based therapy for heart failure. The data also show that NAD⁺-based therapy can be useful in pre-existing heart failure.