Mitochondrial Calcium Signaling in Hepatocyte Health and Disease

Calcium (Ca²⁺) is vital in hepatocyte metabolism and plays a dual role in liver mitochondrial function: Physiological Ca²⁺ stimulates respiration and mitochondrial dynamics-processes crucial for proper metabolic functioning. However, Ca²⁺ overload can be catastrophic, leading to mitochondrial dysfunction and the halt of metabolic processes. This dichotomy plays out in liver diseases such as metabolic dysfunction-associated steatohepatitis (MASH) and alcoholic liver disease (ALD), where excess lipid and alcohol, respectively, result in pathological changes in this precarious Ca²⁺ balance, impairing liver function and contributing to liver failure. In this review, we discuss the complex processes of Ca²⁺ signaling in hepatic mitochondria and how these processes are altered or fail in liver disease states.