Pharmacological modulation of mitochondrial calcium homeostasis

Abstract

Mitochondria are pivotal organelles in calcium (Ca²⁺) handling and signalling, constituting intracellular checkpoints for numerous processes that are vital for cell life. Alterations in mitochondrial Ca²⁺ homeostasis have been linked to a variety of pathological conditions and are critical in the etiology of several human diseases. Efforts have been taken to harness mitochondrial Ca²⁺ transport mechanisms for therapeutic intervention but pharmacological compounds that direct and selectively modulate mitochondrial Ca²⁺ homeostasis are currently lacking. New avenues have however emerged with the breakthrough discoveries on the genetic identification of the main players involved in mitochondrial Ca²⁺ influx and efflux pathways and with recent hints towards a deep understanding of the function of these molecular systems. Here, we review the current advances in the understanding of the mechanisms and regulation of mitochondrial Ca²⁺ homeostasis and its contribution to physiology and human disease. We also introduce and comment on the recent progresses towards a systems-level pharmacological targeting of mitochondrial Ca²⁺ homeostasis.

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