Figure 2.

Pathways to remove stress-damaged macromolecules. The two major degradation pathways in eukaryotes are the ubiquitin-proteasome pathway (UPP) and autophagy. UPP is the degradation pathway for soluble proteins. In response to oxidative stress, it degrades oxidized proteins [15]. Through degradation of the transcription factor nuclear factor-E2-related factor 2 (Nrf2) that is involved in the transcriptional regulation of antioxidant enzymes, the UPP participates in the regulation of the intracellular redox status [41,42]. Autophagy is the name for several degradation pathways. Its best-described form is macroautophagy, the non-selective process of engulfment of cellular material into double membrane vesicles, which are delivered to lysosomes for degradation [43,44]. It has been recently appreciated that autophagy is also selective, called selective autophagy, in which the cargo is recognized by adaptor proteins [45]. Tiny portions of cytoplasm are sequestered and subsequently engulfed by lysosomes in microautophagy [46,47]. This process is well known in yeasts, however, there are not enough data on the mechanisms and physiological relevance of the mammalian microautophagy so far [46]. Chaperone-mediated autophagy (CMA), described only in mammals, delivers selected proteins into lysosomes through specific receptors [48].