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

Abstract

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.

Post‐exercise intramuscular O2 supply is tightly coupled with a higher proximal‐to‐distal ATP synthesis rate in human tibialis anterior

“…2015). It has also been demonstrated that the TA may contain hybrid fibres with different myosin heavy chain expression (Medler, 2019). These different contractile structures may have different post‐exercise requirements for energy recovery.…”

Single-nucleus RNA-seq and FISH identify coordinated transcriptional activity in mammalian myofibers

“…These different Myh isoforms are coded by different genes, and in mammals, fast Myh (fMyh) genes, including Myh2, Myh1, Myh4, embryonic Myh3, neonatal Myh8, and extraocular Myh13 are clustered on a single locus while the slow Myh7 gene lies on another locus 16 . Myofibers can express one, two or three MYH isoforms at the same time at protein and mRNA level [17][18][19][20] . Myofibers expressing more than one MYH isoform are called hybrid fibers in contrast to pure fibers expressing only one isoform.…”

Exercise and the Cisd2 Prolongevity Gene: Two Promising Strategies to Delay the Aging of Skeletal Muscle

“…The fiber type of the quadriceps femoris muscle is IIx/IIb in rodents and IA/IIA and IIA/IIX in humans, which are commonly referred to as fast-twitch fibers. Most other skeletal muscle in limbs, other than the soleus muscle, have a similar fiber type composition both in humans and other mammals [80]. Finally, the quadricep femoris has often been used to study exercise [80] and the effects of aging [77,81,82] in mouse and humans.…”

“…Most other skeletal muscle in limbs, other than the soleus muscle, have a similar fiber type composition both in humans and other mammals [80]. Finally, the quadricep femoris has often been used to study exercise [80] and the effects of aging [77,81,82] in mouse and humans. In agreement with the results on systemic metabolism ( Figure 1B), we found a gender difference in the histology of skeletal muscle, particularly in the Old-Sed mice.…”