D A East
PMI: A Delta Psi(m) Independent Pharmacological Regulator of Mitophagy
East, D A; Fagiani, F; Crosby, J; Georgakopoulos, N D; Bertrand, H; Schaap, M; Fowkes, A; Wells, G; Campanella, M
Authors
F Fagiani
J Crosby
N D Georgakopoulos
H Bertrand
M Schaap
A Fowkes
G Wells
M Campanella
Abstract
Mitophagy is central to mitochondrial and cellular homeostasis and operates via the PINK1/Parkin pathway targeting mitochondria devoid of membrane potential (??m) to autophagosomes. Although mitophagy is recognized as a fundamental cellular process, selective pharmacologic modulators of mitophagy are almost nonexistent. We developed a compound that increases the expression and signaling of the autophagic adaptor molecule P62/SQSTM1 and forces mitochondria into autophagy. The compound, P62-mediated mitophagy inducer (PMI), activates mitophagy without recruiting Parkin or collapsing ??m and retains activity in cells devoid of a fully functional PINK1/Parkin pathway. PMI drives mitochondria to a process of quality control without compromising the bio-energetic competence of the whole network while exposing just those organelles to be recycled. Thus, PMI circumvents the toxicity and some of the nonspecific effects associated with the abrupt dissipation of ??m by ionophores routinely used to induce mitophagy and represents a prototype pharmacological tool to investigate the molecular mechanisms of mitophagy.
Citation
East, D. A., Fagiani, F., Crosby, J., Georgakopoulos, N. D., Bertrand, H., Schaap, M., …Campanella, M. (2014). PMI: A Delta Psi(m) Independent Pharmacological Regulator of Mitophagy. https://doi.org/10.1016/j.chembiol.2014.09.019
Journal Article Type | Article |
---|---|
Acceptance Date | Sep 10, 2014 |
Publication Date | Nov 20, 2014 |
Deposit Date | Jan 16, 2015 |
Publicly Available Date | Nov 21, 2020 |
Journal | Chemistry & Biology |
Peer Reviewed | Peer Reviewed |
Volume | 21 |
Issue | 11 |
Pages | 1585-1596 |
DOI | https://doi.org/10.1016/j.chembiol.2014.09.019 |
Public URL | https://rvc-repository.worktribe.com/output/1404667 |
Files
8813.pdf
(3 Mb)
PDF
You might also like
Ca2+ Transportome and the Interorganelle Communication in Hepatocellular Carcinoma
(2022)
Journal Article
Pharmacological advances in mitochondrial therapy
(2021)
Journal Article
The translocator protein (TSPO) is prodromal to mitophagy loss in neurotoxicity
(2021)
Journal Article
Mitochondria form cholesterol-rich contact sites with the nucleus during retrograde response
(2020)
Journal Article
Mitochondria form contact sites with the nucleus to couple pro-survival retrograde response
(2020)
Journal Article