Mixing it up: the biological significance of hybrid skeletal muscle fibers

Skeletal muscle fibers are classified according to the myosin heavy chain (MHC) isoforms and other myofibrillar proteins expressed within these cells. In addition to 'pure' fibers expressing single MHC isoforms, many fibers are 'hybrids' that co-express two or more different isoforms of MHC or other myofibrillar proteins. Although hybrid fibers have been recognized by muscle biologists for more than three decades, uncertainty persists about their prevalence in normal muscles, their role in fiber-type transitions, and what they might tell us about fiber-type regulation at the cellular and molecular levels. This Review summarizes current knowledge on the relative abundance of hybrid fibers in a variety of muscles from different species. Data from more than 150 muscles from 39 species demonstrate that hybrid fibers are common, frequently representing 25% or more of the fibers in normal muscles. Hybrid fibers appear to have two main roles: (1) they function as intermediates during the fiber-type transitions associated with skeletal muscle development, adaptation to exercise and aging; and (2) they provide a functional continuum of fiber phenotypes, as they possess physiological properties that are intermediate to those of pure fiber types. One aspect of hybrid fibers that is not widely recognized is that fiber-type asymmetries - such as dramatic differences in the MHC composition along the length of single fibers - appear to be a common aspect of many fibers. The final section of this Review examines the possible role of differential activities of nuclei in different myonuclear domains in establishing fiber-type asymmetries.