Fig. 1.8 ). The end products may be released into the cytosol for nutrition or discharged into the extracellular space (exocytosis). In autophagy (left side), senescent organelles or denatured proteins are targeted for lysosome-driven degradation by encircling them with a double membrane derived from the ER and marked by LC3 proteins (microtubule-associated protein 1A/1B-light chain 3). Cell stressors such as nutrient depletion or certain intracellular infections can also activate the autophagocytic pathway. (B) Proteasome degradation. Cytosolic proteins destined for turnover (e.g., transcription factors or regulatory proteins), senescent proteins, or proteins that have become denatured because of extrinsic mechanical or chemical stresses can be tagged by multiple ubiquitin molecules (through the activity of E1, E2, and E3 ubiquitin ligases). This marks the proteins for degradation by proteasomes, cytosolic multisubunit complexes that degrade proteins to small peptide fragments. High levels of misfolded proteins within the ER trigger a protective unfolded protein response engendering a broad reduction in protein synthesis, but specific increases in chaperone proteins that can facilitate protein refolding. If this is inadequate to cope with the levels of misfolded proteins, apoptosis is induced.
mitochondria can undergo regular renewal to stave off contributes the vast majority of cytoplasmic organelles to degenerative changes that might occur because of genetic the fertilized zygote, mitochondrial DNA is virtually disorders or oxygen free radical damage. Mitochondria  entirely maternally inherited. However, because the protein turn over rapidly, with estimated half-lives ranging from 1 constituents of mitochondria derive from both nuclear and to 10 days, depending on the tissue, nutritional status, meta-mitochondrial genetic transcription, mitochondrial disorbolic demands, and intercurrent injury. Because the ovum ders may be X-linked, autosomal, or maternally inherited.
(glucose, glutamine,
ISCHEMIA,
ATP Lipid, protein building blocks
Fig. 1.11 Roles of the mitochondria. Besides the efficient generation of ATP from carbohydrate and fatty acid substrates, mitochondria play an important role in intermediary metabolism, serving as the source of molecules used to synthesize lipids and proteins, and they also are centrally involved in cell life and-death decisions.
Mitochondria provide the enzymatic machinery for oxidative phosphorylation (and thus the relatively efficient generation of energy from glucose and fatty acid substrates). They also have central roles in anabolic metabolism and the regulation programmed cell death, so-called “apoptosis” (
Fig. 1.11