Mitochondrial guardian and therapeutic target: The promise of TFAM in acute kidney injury.
TL;DR
Evidence showing that TFAM upregulation, whether through pharmacological interventions or genetic manipulation, consistently protects against tubular cell injury, preserves mitochondrial function, and attenuates inflammation across diverse AKI models is integrated.
Abstract
Acute kidney injury (AKI) is a clinically significant syndrome characterized by rapid deterioration of renal function. Despite its complex and multifactorial pathogenesis, effective targeted therapies remain scarce. Mitochondrial dysfunction is increasingly recognized as a central driver of AKI progression. Mitochondrial transcription factor A (TFAM), a nucleus-encoded protein that governs mitochondrial DNA (mtDNA) maintenance, transcription and replication, plays an essential role in preserving mitochondrial integrity and biogenesis. This review systematically synthesizes current knowledge on TFAM biology, with a focus on its structural features, regulatory networks, and dynamic changes in the context of AKI. We integrate evidence showing that TFAM upregulation, whether through pharmacological interventions or genetic manipulation, consistently protects against tubular cell injury, preserves mitochondrial function, and attenuates inflammation across diverse AKI models. By providing a conceptual framework that links TFAM's molecular functions to its pathophysiological roles in the kidney, this review highlights TFAM as a promising therapeutic node. We also identify key knowledge gaps and propose future research directions to facilitate the translation of TFAM-targeted strategies into clinical practice.