title: PRKCB/protein kinase C, beta and the mitochondrial axis as key regulators of autophagy.
abstract: Autophagy is the major intracellular system of degradation, and it plays an essential role in various biological events. Recent observations indicate that autophagy is modulated in response to the energy status of the mitochondrial compartment. However, the exact signaling mechanism that controls autophagy under these conditions remains unclear. In this study, we report that the activation of protein kinase C β (PRKCB), a member of the classical PRKCs, negatively modulates the mitochondrial energy status and inhibits autophagy. Furthermore, cells treated with a pharmacological PRKCB inhibitor, and prkcb knockout MEFs showed an increase in autophagy both in vitro and in vivo, as well as an increased mitochondrial membrane potential (Ψm), suggesting a strong involvement of mitochondrial energy in the modulation of the autophagy machinery. Finally, we show that factors that increase the Ψm oppose the PRKCB-dependent inhibition of autophagy. Altogether, these data underscore the importance of PRKCB in the regulation of autophagy; moreover, the finding that a pharmacological modulation of the Ψm modifies autophagy levels may be useful in fighting pathologies (including various types of cancer and neurodegenerative disorders) that are characterized by reduced levels of autophagy.
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine; Section of General Pathology; Interdisciplinary Center for the Study of Inflammation (ICSI); Laboratory for Technologies of Advanced Therapies (LTTA); University of Ferrara; Ferrara, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Patergnani
authors.forename: Saverio
authors.initials: S
authors.lastname: Marchi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rimessi
authors.forename: Massimo
authors.initials: M
authors.lastname: Bonora
authors.forename: Carlotta
authors.initials: C
authors.lastname: Giorgi
authors.forename: Kamal D
authors.initials: KD
authors.lastname: Mehta
authors.forename: Paolo
authors.initials: P
authors.lastname: Pinton
mesh_terms: D000818:Animals; D001343:Autophagy; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000201:enzymology; D057809:HEK293 Cells; D006706:Homeostasis; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D064546:Protein Kinase C beta / Q000172:deficiency / Q000378:metabolism*; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
chemical_list: D020033:Protein Isoforms; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D064546:Protein Kinase C beta
keywords: SHC1/p66; autophagy; calcium; mitochondria; mitochondrial membrane potential; protein kinase C β (PRKCB)