Novel therapeutic strategies targeting mitochondrial quality control for metabolic dysfunction-associated steatotic...

Epidemiological evidence demonstrates that metabolic dysfunction-associated steatotic liver disease (MASLD) has evolved into one of the most widespread chronic liver disorders globally, posing a serious public health challenge. From a mechanistic perspective, the initiation of MASLD is predominantly fueled by multiple factors. Multiple pathological processes, including insulin resistance, oxidative stress, and inflammatory response, are all closely associated with the core issue of mitochondrial dysfunction. Mitochondria, serving as the hub for cellular energy metabolism, exhibit dysfunction that is widely recognized as the key nexus underlying the initiation and progression of MASLD. Maintaining mitochondrial homeostasis is the core mission of the mitochondrial quality control (MQC) system. The MQC system maintains mitochondrial homeostasis by the precise modulation of pathways including mitochondrial biogenesis (MB), mitochondrial dynamics (fusion and fission), and mitophagy. Hence, dysregulation of the MQC system may promote the pathological progression of MASLD. During the MASLD process, continuous metabolic stress disrupts the balance of MQC, and the dysregulation of MQC further exacerbates hepatocyte lipotoxicity damage, forming a vicious cycle. This review elucidates the mechanisms of MQC in MASLD as well as the latest findings. At the same time, we analyze in depth the regulatory mechanisms of each component of MQC and further explored therapeutic strategies of targeting mitochondria.