Possible Involvement of F1F0-ATP synthase and Intracellular ATP in Keratinocyte Differentiation in normal skin and skin lesions

Xie Xiaoyun,Liu Queping,Han Chaofei,Chen Xiang,Chen Chen,Zeng Weiqi,Zhao Shuang,Lu Lixia,Peng Cong,Su Juan

doi:10.1038/srep42672

Abstract

The F1F0-ATP synthase, an enzyme complex, is mainly located on the mitochondrial inner membrane or sometimes cytomembrane to generate or hydrolyze ATP, play a role in cell proliferation. This study focused on the role of F1F0-ATP synthase in keratinocyte differentiation, and its relationship with intracellular and extracellular ATP (InATP and ExATP). The F1F0-ATP synthase β subunit (ATP5B) expression in various skin tissues and confluence-dependent HaCaT differentiation models was detected. ATP5B expression increased with keratinocyte and HaCaT cell differentiation in normal skin, some epidermis hyper-proliferative diseases, squamous cell carcinoma, and the HaCaT cell differentiation model. The impact of InATP and ExATP content on HaCaT differentiation was reflected by the expression of the differentiation marker involucrin. Inhibition of F1F0-ATP synthase blocked HaCaT cell differentiation, which was associated with a decrease of InATP content, but not with changes of ExATP. Our results revealed that F1F0-ATP synthase expression is associated with the process of keratinocyte differentiation which may possibly be related to InATP synthesis.

Highlights

Recent studies have revealed a possible relationship among mitochondrial oxidative metabolism, keratinocyte differeantiation and skin carcinogenisis, in which the underlying mechanisms stay unclear[5]
ATP5B expression is increased with epidermis differentiation in normal skin, some epidermis hyper-proliferative diseases, and squamous cell cancer (SCC) tissues
Expression of ATP5B and K10 was analyzed by IHC in samples from nine normal skin, six chronic dermatitis, five prurigo nodularis, seven keratosis seborrheic, nine verruca vulgaris, 25 psoriasis, five keratoacanthoma, and nine SCC

Summary

Introduction

Recent studies have revealed a possible relationship among mitochondrial oxidative metabolism, keratinocyte differeantiation and skin carcinogenisis, in which the underlying mechanisms stay unclear[5]. Oligomycin, an antibiotic produced by Streptomyces diastatochromogens, can bind to the F0 sector, and inhibit the InATP synthesis and hydrolysis[21]; while another inhibitor, piceatannol, mainly inhibits the ExATP synthesis under normal curlture conditions by interacting with the F1 sector[22,23]. These inhibitors provide us ways to regulate the functioning status of F1F0-ATP synthase and the InATP and ExATP content, to explore its downstream effects. Results of the present study could help to determine new targets for the treatment of aberrant keratinocyte proliferation diseases

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