The Emerging Role of the Mitochondrial Respiratory Chain in Skeletal Aging

Abstract

Maintenance of mitochondrial homeostasis is crucial for ensuring healthy mitochondria and normal cellular function. This process is primarily responsible for regulating processes that include mitochondrial OXPHOS, which generates ATP, as well as mitochondrial oxidative stress, apoptosis, calcium homeostasis, and mitophagy. Bone mesenchymal stem cells express factors that aid in bone formation and vascular growth. Positive regulation of hematopoietic stem cells in the bone marrow affects the differentiation of osteoclasts. Furthermore, the metabolic regulation of cells that play fundamental roles in various regions of the bone, as well as interactions within the bone microenvironment, actively participates in regulating bone integrity and aging. The maintenance of cellular homeostasis is dependent on the regulation of intracellular organelles, thus understanding the impact of mitochondrial functional changes on overall bone metabolism is crucially important. Recent studies have revealed that mitochondrial homeostasis can lead to morphological and functional abnormalities in senescent cells, particularly in the context of bone diseases. Mitochondrial dysfunction in skeletal diseases results in abnormal metabolism of bone-associated cells and a secondary dysregulated microenvironment within bone tissue. This imbalance in the oxidative system and immune disruption in the bone microenvironment ultimately leads to bone dysplasia. In this review, we examine the latest developments in mitochondrial respiratory chain regulation and its impacts on maintenance of bone health. Specifically, we explored whether enhancing mitochondrial function can reduce the occurrence of bone cell deterioration and improve bone metabolism. These findings offer prospects for developing bone remodeling biology strategies to treat age-related degenerative diseases.

Consequences of Aging on Bone

“…Disruption of mitochondrial respiratory chain transmission can disrupt mitochondrial homeostasis, which results in an adverse bone phenotype. This dysfunction is a major cause of bone aging and metabolic imbalance [211]. Mitochondrial energy metabolism in BMSCs maintains their viability, osteogenic ability, and lipid-forming potential [212].…”

Lack of Mitochondrial DNA Provides Metabolic Advantage in Yeast Osmoadaptation

“…However, it is well known that mitochondria also control a variety of other cellular functions including amino acid, nucleotide, lipid and heme biosynthesis; the redox state; genomic stability and active stress responses ultimately determining the fate of the cell. In line with the multifaceted role of these organelles, alterations in mitochondrial function have been linked to many human pathologies ranging from rare genetic disorders to common diseases, such as neurodegeneration [ 1 ], cancer [ 2 , 3 , 4 ] and the aging process itself [ 5 , 6 , 7 , 8 , 9 ].…”