title: Mitochondrial Complexes I and II Are More Susceptible to Autophagy Deficiency in Mouse β-Cells.
abstract: BACKGROUND
  Damaged mitochondria are removed by autophagy. Therefore, impairment of autophagy induces the accumulation of damaged mitochondria and mitochondrial dysfunction in most mammalian cells. Here, we investigated mitochondrial function and the expression of mitochondrial complexes in autophagy-related 7 (Atg7)-deficient β-cells.
  
  
  METHODS
  To evaluate the effect of autophagy deficiency on mitochondrial function in pancreatic β-cells, we isolated islets from Atg7(F/F):RIP-Cre+ mice and wild-type littermates. Oxygen consumption rate and intracellular adenosine 5'-triphosphate (ATP) content were measured. The expression of mitochondrial complex genes in Atg7-deficient islets and in β-TC6 cells transfected with siAtg7 was measured by quantitative real-time polymerase chain reaction.
  
  
  RESULTS
  Baseline oxygen consumption rate of Atg7-deficient islets was significantly lower than that of control islets (P<0.05). Intracellular ATP content of Atg7-deficient islets during glucose stimulation was also significantly lower than that of control islets (P<0.05). By Oxygraph-2k analysis, mitochondrial respiration in Atg7-deficient islets was significantly decreased overall, although state 3 respiration and responses to antimycin A were unaffected. The mRNA levels of mitochondrial complexes I, II, III, and V in Atg7-deficient islets were significantly lower than in control islets (P<0.05). Down-regulation of Atg7 in β-TC6 cells also reduced the expression of complexes I and II, with marginal significance (P<0.1).
  
  
  CONCLUSIONS
  Impairment of autophagy in pancreatic β-cells suppressed the expression of some mitochondrial respiratory complexes, and may contribute to mitochondrial dysfunction. Among the complexes, I and II seem to be most vulnerable to autophagy deficiency.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Korea.; Department of Internal Medicine, Korea Cancer Center Hospital, Korea.
authors.forename: Min Joo
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Innovative Research Institute for Cell Therapy, Seoul, Korea.
authors.forename: Ok Kyong
authors.initials: OK
authors.lastname: Choi
authors.affiliation: Innovative Research Institute for Cell Therapy, Seoul, Korea.
authors.forename: Kyung Sil
authors.initials: KS
authors.lastname: Chae
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Korea.
authors.forename: Min Kyeong
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Korea.
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Komatsu
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Innovative Research Institute for Cell Therapy, Seoul, Korea.
authors.forename: Hakmo
authors.initials: H
authors.lastname: Lee
authors.affiliation: Innovative Research Institute for Cell Therapy, Seoul, Korea.
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Chung
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Korea.
authors.forename: Soo Heon
authors.initials: SH
authors.lastname: Kwak
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Korea.
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Korea. junghs@snu.ac.kr.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Jung
keywords: Autophagy; Insulin-secreting cells; Mitochondria; Mitochondrial complex