Under the ROS…thiol network is the principal suspect for autophagy commitment.
Low molecular weight and protein sulphydryls undergo reactive oxygen species (ROS)-mediated oxidation. However, in contrast to the irreversible damages that oxidative conditions yield on biomolecules, the oxidation of reactive cysteines frequently results in reversible modifications, which represent the prototype of the molecular mechanisms underlying redox signaling. Many proteins involved in a wide range of cellular processes have been classified as “redoxsensitive,” thereby modulating their function/activity dependent on the redox state of their critical thiols. Growing evidence from the past few years supports the idea that ROS production also correlates with the occurrence of autophagy. Nonetheless, the cysteine protease Atg4 remains the sole example of a protein whose redox regulation has been completely characterized and demonstrated to be necessary for the progression of autophagy. The principal aim of this commentary is to draw attention to the remarkable number of proteins that can fit the double role of: (i) being involved in autophagy, especially in autophagosome formation and (ii) sensing alterations of the cellular redox state by means of reactive cysteine residues. We will also attempt to provide a hypothetical model to explain the possible functional role of thiols in the occurrence of autophagy and outline a network of redox reactions likely concurring to allow the correct initiation and completion of autophagosomes.
Filomeni
Giuseppe
G
Department of Biology, University of Rome Tor Vergata, via della Ricerca Scientifica, Rome, Italy. filomeni@bio.uniroma2.it
Desideri
Enrico
E
Cardaci
Simone
S
Rotilio
Giuseppe
G
Ciriolo
Maria Rosa
MR
D001343:Autophagy / Q000502:physiology*; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism
D006360:Heat-Shock Proteins; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D054464:Peroxiredoxins; D043743:Ubiquitin-Protein Ligase Complexes; D020691:rab GTP-Binding Proteins; D003545:Cysteine