Characterization of Allograft Inflammatory Factor 1-Like (Aif1L) in Skeletal Muscle

Skeletal muscle wasting, or atrophy, results from decreased protein synthesis and an associated increase in protein degradation. This shift towards a decrease in protein content of the cell can result from various physiological conditions, including immobilization, denervation, and aging. Muscle RING Finger 1 (MuRF1), an E3 ubiquitin ligase, has been found to be upregulated during almost all conditions of muscle wasting and is believed to play an important role in targeting proteins for degradation. However, preliminary data described in this study provides new evidence that MuRF1’s role in the skeletal muscle atrophy cascade is likely more complex and it appears that MuRF1 is necessary for full transcriptional activation of a small subset of neurogenic atrophy-induced genes, including allograft inflammatory factor 1-like (Aif1L). Aif1L has been identified as a novel skeletal muscle gene that is upregulated in wild-type mice, while MuRF1-null mice show blunted upregulation in response to denervation. Aif1L is predicated to contain two EF-hand domains, which can act as calcium ion binding domains. Furthermore, Aif1L has also recently been implicated in regulating actomyosin contractility and filopodial extensions and may play a similar role in muscle cells. Quantitative PCR was used to assess the expression levels in cultured muscle cells and confirmed expression during proliferation and increased expression during differentiation. Aif1L was ectopically expressed in the presence of a reporter plasmid with an AP-1 consensus element revealing no inhibition of MAP Kinase signaling. Interestingly, analysis via Western blot, showed significant p-ERK inhibition and attenuation of MyHC expression suggesting Aif1L may influence muscle cell differentiation. The results presented here in combination with additional research into the regulation and function of Aif1L will help contribute new insight into the molecular genetic mechanisms of skeletal muscle atrophy and may provide a better understanding of how MuRF1 may regulate the neurogenic atrophy cascade during muscle wasting. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.