Kruppel-Like Factor 4 (KLF4) and its Regulation on Mitochondrial Homeostasis

Abstract

Mitochondria are vital organelles that supply ATP and other energy metabolites to meet the bioenergetics demands of the cell. In environments of stress or increased energy requirement, mitochondria are highly dynamic and can undergo biogenesis, fusion/fission, or autophagy. The transcription factor family, Kruppel-Like Factor (KLF), is necessary to carry out normal cellular processes from proliferation to differentiation. Recently, its importance in metabolic homeostasis in various tissue types has gained much attention. A handful of evidence supports KLF4’s involvement in regulating mitochondrial homeostasis in both healthy and cancer cells. In this review, we aim to summarize the available literature that demonstrates KLF4’s ability to modulate the mitochondrial life cycle in: Cardiac tissue, in which KLF4-knockdown subsequently leads to Heart Failure (HF), and Glioblastoma (GBM), where its expression promotes extensive mitochondrial fusion and offers mild cell protection under serum-deprivation

Exploring the dermotoxicity of the mycotoxin deoxynivalenol: combined morphologic and proteomic profiling of human epidermal cells reveals alteration of lipid biosynthesis machinery and membrane structural integrity relevant for skin barrier function

“…In addition to its role in sustaining skin barrier function, Klf4 plays a central role in the regulation of metabolism and in particular mitochondrial homeostasis (Tung and Xia 2018). In line, among the most specifically challenged organelles after DON treatment, mitochondria were outstanding.…”

SP and KLF Transcription Factors in Cancer Metabolism

“…KLF4 expression in cells under stress caused an increase in oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Thus, in gliomas, KLF4 plays a role in recovering energy metabolism ( Figure 7 ) [ 110 , 111 ].…”

Danon Disease-Associated LAMP-2 Deficiency Drives Metabolic Signature Indicative of Mitochondrial Aging and Fibrosis in Cardiac Tissue and hiPSC-Derived Cardiomyocytes

“…As underpinned by the data processing with the bioinformatics tool oPOSSUM, the regulatory events in Danon patients could be retraced to three main transcription factors ( Figure 1 E). In addition to the abovementioned PPRG:RXRA, KLF4 was recently described to regulate cardiac mitochondria homeostasis [ 30 ] and pro-inflammatory fibrotic injury response [ 31 ]. Similarly, SP1 was described as a key player in the induction of cardiac/cardiomyocyte fibrosis [ 29 , 62 ].…”

“…Intriguingly, these three transcription factors underpin intensive regulation of the morphological and metabolic adaptation strategies. PPARs are crucial regulators of glucose and lipid metabolism [27], SP-1 is involved in response to hypoxia [28,29] and KLF4 sustains inflammation and mitochondrial metabolic adaptation [30][31][32] and promotes senescence [33]. Indeed, mitochondria are central in determining aging phenotypes and associated metabolic states [34].…”