The emerging role of PKM in keratinocyte homeostasis and pathophysiology

Abstract

Increased aerobic glycolysis in keratinocytes has been reported as a hallmark of skin diseases while its pharmacological inhibition restores keratinocyte homeostasis. Pyruvate kinase muscle (PKM) isoforms are key enzymes in the glycolytic pathway and, therefore, an attractive therapeutic target. Simon Nold and colleagues used CRISPR/Cas9‐mediated gene editing to investigate the outcomes of PKM splicing perturbations and specific PKM1 or PKM2 deficiency in human HaCaT keratinocytes. Collectively, the study demonstrated different effects of PKM1 or PKM2 depletion on the reciprocal PKM isoform and on keratinocyte gene expression, metabolism and proliferation. Findings from this study provide novel insights into the role of PKM in keratinocyte homeostasis, warranting additional investigations into the underlying molecular mechanisms and potential therapeutic applications.

Discovery of Oogenesis Biomarkers from Mouse Oocytes Using a Single-Cell Proteomics Approach

“…The abundances of hexokinase-1 (HK1), 6-phosphofructokinase (PFKL), and glucose-6-phosphate isomerase (GPI) increased by 500-, 2.40-, and 1.30-fold in aged oocytes, while the abundances of fructose-bisphosphate aldolase A (ALDOA), bisphosphoglycerate mutase (BPGM), α-enolase (ENO1), and pyruvate kinase (PKM) decreased by 1.26-, 6.43-, 1.39-, and 2.11-fold in aged oocytes (Table S3). These proteins are reported to be the rate-limiting enzymes in glycolysis. − The dysregulation of these proteins indicated impaired glycolysis in aged oocytes, which results in reduced energy production and vitality. Interestingly, the expressions of enzymes involved in fructose-6-phosphate metabolism, HK1, GPI, and PFKL, were upregulated in aged oocytes.…”

Unravelling the complexity of enzyme catalysis

“…In a second Commentary article, on keratinocytes and skin diseases, Jenna Demeter and colleagues comment on the work of Simon Nold et al . (also included in this Focus Issue), referring to the potential of pyruvate kinase muscle isoforms as therapeutic targets [12,13]. They overview the effects of isoform depletion on keratinocyte homeostasis, and implications for cellular mechanisms and therapy.…”

“…In their Commentary article [10], Kv eta Tr avn ı ckov a and Kvido St r ı sovsk y discuss the work of Moritz Ballin et al [11] (also collected in this Focus Issue), which implicates SPPL2a/b intramembrane proteases in the cleavage of SNARE proteins and thereby regulation of SNARE protein turnover. In a second Commentary article, on keratinocytes and skin diseases, Jenna Demeter and colleagues comment on the work of Simon Nold et al (also included in this Focus Issue), referring to the potential of pyruvate kinase muscle isoforms as therapeutic targets [12,13]. They overview the effects of isoform depletion on keratinocyte homeostasis, and implications for cellular mechanisms and therapy.…”