Cited by 55Autophagy in Disease and TherapyMetabolism, Diabetes, and CancerCalcium signaling and nucleotide metabolism

CCCP induces autophagy in an AMPK-independent manner

Kwon, Kyum-Yil, Viollet, Benoit, Yoo, Ook Joon·2011·Biochemical and Biophysical Research Communications

Abstract

AMP-activated protein kinase (AMPK) is an important sensor of cellular energy status, and is involved in cell growth and autophagy through mammalian target of rapamycin complex 1 (mTORC1). Carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler, leads to AMPK activation and Parkin-dependent mitophagy, respectively. However, the detailed biochemical mechanism of how CCCP induces autophagy or mitophagy has not been investigated yet. Here, we showed that CCCP inhibits mTORC1 independently of AMPK, although CCCP induces AMPK activation. Using wild type (WT) and AMPKα1/α2 double knockout (DKO) MEFs, we observed that CCCP promotes endogenous LC3 lipidation and formation of RFP-LC3 puncta, indicating autophagosome or autolysosome, in an AMPK-independent manner. Finally, we also revealed that the percentage of CCCP-dependent colocalization between mitochondria and RFP-LC3 puncta is similar both in WT and AMPKα1/α2 DKO MEFs. Based on these data, we concluded that AMPK is not essential in regulation of CCCP-induced autopahgy including mitophagy.

Integrity signals

Registry

Crossref · 10.1016/j.bbrc.2011.11.038

Cites

22 of 22 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The positive effect of mitochondrial uncoupling on autophagy has been established in many cellular and animal models, including adipocytes, MEFs, HeLa cells, HepG2 cells, SH-SY5Y neuroblastoma cells, and C57BL6 mice.

    “The positive effect of mitochondrial uncoupling on autophagy has been established in many cellular and animal models, including adipocytes [91], MEFs [92], HeLa cells [93], HepG2 cells [90], SH-SY5Y neuroblastoma cells [93], or C57BL6 mice [94].”
  • CCCP inhibits mTORC1 independently of AMPK.

    “The role of AMPK activation, in response to a decrease in the ATP/AMP ratio caused by mitochondrial uncoupling as a requirement for mitophagy activation, has been questioned as CCCP is able to inhibit the activity of mTORC1 independently of AMPK [92].”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Kwon, K.-Y., Viollet, B., & Yoo, O. J.
Affiliations
Korea Advanced Institute of Science and Technology (KR)
Corresponding author
Yoo, Ook Joon
Venue
Biochemical and Biophysical Research Communications
Publisher
Elsevier BV
Published
2011-12
Volume
416
Issue
3-4
Pages
343-348
ISSN
0006-291X (ISSN-L)
OpenAlex
W2045081864
Cited by
55
References
22
Citations by year
2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 7 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 5 · 2015: 11 · 2014: 1 · 2013: 6 · 2012: 1
FWCI
1.93
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemical and Biophysical Research Communications (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
CCCP, autophagy, AMPK, mTORC1, mitophagy, mitochondrial uncouplers, LC3 lipidation
MeSH terms
Mechanistic Target of Rapamycin Complex 1, AMP-Activated Protein Kinase Kinases, Animals, Autophagy, Carbonyl Cyanide m-Chlorophenyl Hydrazone, Humans, Protein Kinases, Proteins, Mice, Knockout, Multiprotein Complexes, Mice, HEK293 Cells, TOR Serine-Threonine Kinases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review