Transforming growth factor-β, bioenergetics, and mitochondria in renal disease

The transforming growth factor-β (TGF-β) family comprises more than 30 family members that are structurally related secreted dimeric cytokines, including TGF-β, activins, and bone morphogenetic proteins/growth and differentiation factors. TGF-β are pluripotent regulators of cell proliferation, differentiation, apoptosis, migration, and adhesion of many different cell types. TGF-β pathways are highly evolutionarily conserved and control embryogenesis, tissue repair, and tissue homeostasis in invertebrates and vertebrates. Aberrations in TGF-β activity and signaling underlie a broad spectrum of developmental disorders and major pathologies in human beings, including cancer, fibrosis, and autoimmune diseases. Recent observations have indicated an emerging role for TGF-β in the regulation of mitochondrial bioenergetics and oxidative stress responses characteristic of chronic degenerative diseases and aging. Conversely, energy and metabolic sensory pathways cross-regulate mediators of TGF-β signaling. Here, we review TGF-β and regulation of bioenergetic and mitochondrial functions, including energy and oxidant metabolism and apoptotic cell death, as well as their emerging relevance in renal biology and disease.