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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


D A East

F Fagiani

J Crosby

N D Georgakopoulos

H Bertrand

M Schaap

A Fowkes

G Wells

M Campanella


Mitophagy is central to mitochondrial and cellular homeostasis and operates via the PINK1/Parkin pathway targeting mitochondria devoid of membrane potential (ΔΨm) 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 ΔΨm 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 ΔΨm by ionophores routinely used to induce mitophagy and represents a prototype pharmacological tool to investigate the molecular mechanisms of mitophagy.


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.

Journal Article Type Article
Acceptance Date Sep 10, 2014
Publication Date Nov 20, 2014
Deposit Date Jan 16, 2015
Publicly Available Date Jan 16, 2015
Journal Chemistry & Biology
Peer Reviewed Peer Reviewed
Volume 21
Issue 11
Pages 1585-1596
Public URL


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