Genes involved in the regulation of different types of autophagy and their participation in cancer pathogenesis

// Martyna Bednarczyk 1 , Nikola Zmarzly 2 , Beniamin Grabarek 2 , Urszula Mazurek 2 and Malgorzata Muc-Wierzgon 1 1 Department of Internal Diseases, School of Public Health in Bytom, Medical University of Silesia in Katowice, 40–055 Katowice, Poland 2 Department of Molecular Biology, School of Pharmacy with The Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, 40–055 Katowice, Poland Correspondence to: Martyna Bednarczyk, email: martyna.bednarczyk@outlook.com Keywords: autophagy; lysosome; chaperones; mitochondria; cancer Received: March 15, 2018      Accepted: August 30, 2018      Published: September 28, 2018 ABSTRACT Autophagy is a highly conserved mechanism of self-digestion that removes damaged organelles and proteins from cells. Depending on the way the protein is delivered to the lysosome, four basic types of autophagy can be distinguished: macroautophagy, selective autophagy, chaperone-mediated autophagy and microautophagy. Macroautophagy involves formation of autophagosomes and is controlled by specific autophagy-related genes. The steps in macroautophagy are initiation, phagophore elongation, autophagosome maturation, autophagosome fusion with the lysosome, and proteolytic degradation of the contents. Selective autophagy is macroautophagy of a specific cellular component. This work focuses on mitophagy (selective autophagy of abnormal and damaged mitochondria), in which the main participating protein is PINK1 (phosphatase and tensin homolog-induced putative kinase 1). In chaperone-mediated autophagy, the substrate is bound to a heat shock protein 70 chaperone before it is delivered to the lysosome. The least characterized type of autophagy is microautophagy, which is the degradation of very small molecules without participation of an autophagosome. Autophagy can promote or inhibit tumor development, depending on the severity of the disease, the type of cancer, and the age of the patient. This paper describes the molecular basis of the different types of autophagy and their importance in cancer pathogenesis.