[Role of mitochondria in osteoclast function]

Abstract

Mitochondria, membrane-enclosed structures found in most eukaryotic cells, generate most of the cell's supply of ATP, used as a source of chemical energy. In addition to supplying cellular energy, mitochondria are involved in signaling, cellular differentiation, cell death, and the aging process. Osteoclasts, highly differentiated bone-resorbing cells of hematopoietic origin, have two conflicting tendencies : a lower capacity to survive and a higher capacity to execute energy-consuming activities such as bone resorption. We here highlight the role of mitochondria in osteoclast function. Recent studies have revealed that ATP depletion following Tfam (mitochondrial transcription factor A) deficiency leads to increased bone-resorbing activity despite accelerated apoptosis, and the release of endogenous ATP negatively regulates osteoclast function through an autocrine/paracrine feedback loop. These findings provide evidence for a previously unknown mechanism by which mitochondria regulate the inverse correlation between osteoclast survival and bone resorption.