4-phenylbutyric acid alleviated sepsis-induced myocardial dysfunction by inhibition of MAM formation to improve mitochondrial dynamic balance in myocardial cells

Description

Yue Wu and colleagues tested a compound that may shield the heart during sepsis, when infection-driven organ failure raises death risk. Published in 2026, the study used animal and cell models of sepsis, treating with 4-phenylbutyric acid, a drug known to ease endoplasmic reticulum stress. Transcript data from septic patients had pointed to that stress pathway as central to sepsis-related heart dysfunction.

The compound markedly eased heart dysfunction by curbing the formation of junctions between endoplasmic reticulum and mitochondria and restoring mitochondrial balance and function. It acted by binding two catalytic sites on an enzyme called HK2, cutting glycolysis and lactate buildup, which in turn reduced a protein modification that drives junction assembly. The authors propose a new treatment chain for septic heart injury. Readers get a mechanistic lead, still preclinical.

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Source: https://europepmc.org/articles/PMC13526368