Senescent organelles and large protein complexes can be shuttled into lysosomes by a process called autophagy. Through poorly understood mechanisms, obsolete organelles are corralled by a double membrane derived from the ER; the membrane progressively expands to encircle a collection of structures and forms an autophagosome, which then fuses with lysosomes where the contents are catabolized. In addition to facilitating the turnover of aged and defunct cellular constituents, autophagy also is used to preserve cell viability during nutrient depletion. The significance of autophagy in cell biology was recognized by the award of the 2016 Nobel Prize to Yoshinori Ohsumi for his discoveries relating to the mechanism of autophagy. This topic is discussed in more detail in Chapter 2.
Phagocytosis of microorganisms or large fragments of matrix or debris occur primarily in professional phagocytes (macrophages and neutrophils). The material is engulfed to form a phagosome that subsequently fuses with a lysosome.
Fig. 1.10 ); these include denatured or misfolded proteins (akin to what occurs within the ER), as well as other proteins whose levels and half-life need to be tightly regulated (e.g., transcription factors). Many (but not all) proteins destined for proteasome destruction are targeted after covalent addition of a protein called ubiquitin. Polyubiquitinated molecules are progressively unfolded and funneled into the polymeric proteasome complex, a cylinder containing multiple different protease activities, each with its active site pointed at the hollow core. Proteasomes digest proteins into small (6–12 amino acids) fragments that can subsequently be further degraded to their constituent amino acids and recycled, or presented to immune cells in the context of major histocompatibility complex class I molecules, an important component of host immune surveillance.
Mitochondria evolved from ancestral prokaryotes that were engulfed by primitive eukaryotes about 1.5 billion years ago. Their origin explains why mitochondria contain their own DNA genome (circularized, about 1% of the total cellular DNA), which encodes roughly 1% of the total cellular proteins and approximately 20% of the proteins involved in oxidative phosphorylation. Although their genomes are small, mitochondria can nevertheless perform all the steps of DNA replication, transcription, and translation. Interestingly, the mitochondrial machinery is similar to present-day bacteria; for example, mitochondria initiate protein synthesis with N-formylmethionine and are sensitive to anti-bacterial antibiotics.
Mitochondria are dynamic, constantly undergoing fission and fusion with other mitochondria; in this way, http://ebooksmedicine.net
Fig. 1.10 Intracellular catabolism. (A) Lysosomal degradation. In heterophagy (right side), lysosomes fuse with endosomes or phagosomes to facilitate the degradation of their internalized contents (see