Inhibition of the AMPK/PGC-1α/Mfn2 Axis is Associated with Mitochondria-Endoplasmic Reticulum Dysfunction and Ultrastructural Remodeling in a Rat Model of Myofascial Trigger Points [Letter]

Abstract

We read with great interest the recent study by Yu et al published in your journal. 1 To our knowledge, this is the first study to systematically examine the AMPK/PGC-1α/Mfn2 signaling axis in a rat model of myofascial trigger points (MTrPs) and the first to document an increased frequency of mitochondria-endoplasmic reticulum contacts (MERCs) in the MTrPs region by transmission electron microscopy. The authors established the active MTrPs model by electro-myography and palpation and integrated histological, ultrastructural, and molecular evidence within a unified framework, providing valuable clues for the “energy crisis” hypothesis. We commend this multilevel study design. On this basis, we would like to raise three points for discussion, with a view to further strengthening the evidentiary chain in this field. First, the directional discrepancy between Mfn2 downregulation and increased MERCs warrants attention as a scientific question in its own right. In the Introduction, the authors adopted the canonical model in which Mfn2 acts as a tethering protein at MERCs; under this model, Mfn2 downregulation would be expected to reduce mitochondria-endoplasmic reticulum contacts, 2 whereas the authors observed an increase. The authors reconciled this discrepancy by invoking an “ineffective compensatory response”, whereby cells increase organelle contacts