RT Journal Article
T1 MTORC1 Regulates both General Autophagy and Mitophagy Induction after Oxidative Phosphorylation Uncoupling
A1 Bartolomé, Alberto
A1 García Aguilar, Ana
A1 Asahara, Shun-Ichiro
A1 Yoshiaki, Kido
A1 Guillén, Carlos
A1 Guillén Viejo, Carlos
A1 Pajvani, Utpal B
A1 Benito De Las Heras, Manuel R.
AB Mechanistic target of rapamycin complex 1 (MTORC1) is a critical negative regulator of general autophagy. We hypothesized that MTORC1 may specifically regulate autophagic clearance of damaged mitochondria. To test this, we used cells lacking tuberous sclerosis complex 2 (TSC2-/- cells), which show constitutive MTORC1 activation. TSC2-/- cells show MTORC1-dependent impaired autophagic flux after chemical uncoupling of mitochondria, increased mitochondrial-protein aging, and accumulation of p62/SQSTM1-positive mitochondria. Mitochondrial autophagy (mitophagy) was also deficient in cells lacking TSC2, associated with altered expression of PTEN-induced putative kinase 1 (PINK1) and PARK2 translocation to uncoupled mitochondria, all of which were recovered by MTORC1 inhibition or expression of constitutively active forkhead box protein O1 (FoxO1). These data prove the necessity of intact MTORC1 signaling to regulate two synergistic processes required for clearance of damaged mitochondria: (i) general autophagy initiation and (ii) PINK1/PARK2-mediated selective targeting of uncoupled mitochondria to the autophagic machinery
PB Taylor & Francis
YR 2017
FD 2017-12-01
LK https://hdl.handle.net/20.500.14352/115432
UL https://hdl.handle.net/20.500.14352/115432
LA eng
NO Bartolomé A, García-Aguilar A, Asahara SI, Kido Y, Guillén C, Pajvani UB, Benito M. MTORC1 Regulates both General Autophagy and Mitophagy Induction after Oxidative Phosphorylation Uncoupling. Mol Cell Biol. 2017 Nov 13;37(23):e00441-17. doi: 10.1128/MCB.00441-17. PMID: 28894028; PMCID: PMC5686580
NO Ministry of Education, Culture, Sports, Science and Technology, Japan
NO Ministerio de Economía, Industria y Competitividad (España)
NO National Institutes of Health
DS Docta Complutense
RD 27 dic 2025