Studies of alternative macroautophagy and its application for "Autophagic Diseases"

2014 Fiscal Year Final Research Report

• Project/Area Number: 22229002
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: SHIMIZU Shigeomi 東京医科歯科大学, 難治疾患研究所, 教授 (70271020)
• Co-Investigator(Kenkyū-buntansha): KONISHI Akimitsu 東京医科歯科大学, 難治疾患研究所, 講師 (50381877) ; YOSHIDA Tatsushi 東京医科歯科大学, 難治疾患研究所, 講師 (80315936)
• Co-Investigator(Renkei-kenkyūsha): ARAKAWA Satoko 東京医科歯科大学, 難治疾患研究所, 助教 (90415159)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: オートファジー / Atg5非依存性 / がん / 神経変性疾患 / 発生

Outline of Final Research Achievements

Autophagy is a process that leads to the bulk degradation of subcellular constituents through the creation of autophagosomes/ autolysosomes. Previously, it was believed that Atg5 is essential for induction of autophagy. However, we found that cells lacking Atg5 can still induce autophagy. Therefore, we here analyzed Atg5-independent alternative autophagy. We first discovered that alternative autophagy is conserved phylogenetically from yeast to mammals. We next identified 14 novel genes that are required for alternative autophagy and unveiled the molecular mechanisms. Using 11 different types of alternative autophagy-deficient mice, we discovered the involvement of alternative autophagy in the development and cell differentiation. We also identified the defect of alternative autophagy causes various diseases, including cancer and neurodegenerative diseases. We further discovered autophagy-inducing small compounds for applying “Autophagy Diseases”

Free Research Field

細胞生物学