Figure 8
From: Plekhm2 acts as an autophagy modulator in murine heart and cardiofibroblasts
Postulated role of Plekhm2 in the murine vs. the human heart. Young PLK2-KO mice exhibit no difference in cardiac function or autophagy markers but demonstrate higher basal Akt phosphorylation. Growth retardation was observed following starvation and in old PLK2-KO mice (12-month-old). Impaired autophagy was also noted in vitro in PLK2-KO cardiofibroblasts but not in cardiomyocytes. Overall, the absence of Plekhm2 in mice appears to promote compensatory mechanism(s) enabling the heart to manage functionally even in the presence of neurohormonal stress without detrimental consequences. Importantly, while PLEKHM2 loss of function mutations are clearly associated with a DCM phenotype in human9,16 and autophagy derangement in patient's primary fibroblast9 as well as in iPSC-induced cardiomyocytes17,46, autophagy derangement could not be identified in murine cardiomyocytes. Whether this overt difference explains the absence of DCM phenotype in the PLK2-KO mice remains to be determined. Figure was created with BioRender.com.
