Role of NADPH oxidase in the regulation of autophagy in cardiomyocytes

Sebastiano Sciarretta, Derek Yee, Paul Ammann, Narayani Nagarajan, Massimo Volpe, Giacomo Frati, Junichi Sadoshima

Research output: Contribution to journalReview article

20 Scopus citations

Abstract

In the past several years, it has been demonstrated that the reactive oxygen species (ROS) may act as intracellular signalling molecules to activate or inhibit specific signalling pathways and regulate physiological cellular functions. It is now well-established that ROS regulate autophagy, an intracellular degradation process. However, the signalling mechanisms through which ROS modulate autophagy in a regulated manner have only been minimally clarified. NADPH oxidase (Nox) enzymes are membrane-bound enzymatic complexes responsible for the dedicated generation of ROS. Different isoforms of Nox exist with different functions. Recent studies demonstrated that Nox-derived ROS can promote autophagy, with Nox2 and Nox4 representing the isoforms of Nox implicated thus far. Nox2- and Nox4-dependent autophagy plays an important role in the elimination of pathogens by phagocytes and in the regulation of vascular- and cancer-cell survival. Interestingly, we recently found that Nox is also important for autophagy regulation in cardiomyocytes. We found that Nox4, but not Nox2, promotes the activation of autophagy and survival in cardiomyocytes in response to nutrient deprivation and ischaemia through activation of the PERK (protein kinase RNA-like endoplasmic reticulum kinase) signalling pathway. In the present paper, we discuss the importance of Nox family proteins and ROS in the regulation of autophagy, with a particular focus on the role of Nox4 in the regulation of autophagy in the heart.

Original languageEnglish
Pages (from-to)387-403
Number of pages17
JournalClinical Science
Volume128
Issue number7
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Keywords

  • Autophagy
  • Cardiomyocyte
  • NAPDH oxidase
  • Reactive oxygen species

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    Sciarretta, S., Yee, D., Ammann, P., Nagarajan, N., Volpe, M., Frati, G., & Sadoshima, J. (2015). Role of NADPH oxidase in the regulation of autophagy in cardiomyocytes. Clinical Science, 128(7), 387-403. https://doi.org/10.1042/CS20140336