Mitochondria degradation

Glutathione peroxidase Cytoplasm, Mitochondria Degradation of H2O2 and lipoperoxides... 

A DNase treatment (Nass, 1969a) also reduces contamination by nuclear DNA since generally DNase cannot enter intact mitochondria. Degradation of mt DNA by DNase may occur in damaged or leaky mitochondria. 

A variety of protein import pathways into the vacuole are known (Burd et al., 1998 Bryant and Stevens, 1998). It includes the sorting from the Golgi apparatus, endocytosis, autophagy (where a part of the cytoplasm such as a mitochondrion is engulfed into a newly formed vacuole and is degraded), direct import from the cytosol, and the vacuolar inheritance from the mother cell. Of these, the pathways from the Golgi... 

We directed our initial attention to the mitochondrion-specific phospholipid, cardiolipin because it is particularly rich in polyunsaturated fatty acids which are vulnerable to oxidative attack. It seemed reasonable to speculate that mitochondrial cardiolipin may degrade by the enhanced peroxidation reactions during apoptotic cell death,... 

The tricarboxylic acid cycle not only takes up acetyl CoA from fatty acid degradation, but also supplies the material for the biosynthesis of fatty acids and isoprenoids. Acetyl CoA, which is formed in the matrix space of mitochondria by pyruvate dehydrogenase (see p. 134), is not capable of passing through the inner mitochondrial membrane. The acetyl residue is therefore condensed with oxaloacetate by mitochondrial citrate synthase to form citrate. This then leaves the mitochondria by antiport with malate (right see p. 212). In the cytoplasm, it is cleaved again by ATP-dependent citrate lyase [4] into acetyl-CoA and oxaloacetate. The oxaloacetate formed is reduced by a cytoplasmic malate dehydrogenase to malate [2], which then returns to the mitochondrion via the antiport already mentioned. Alternatively, the malate can be oxidized by malic enzyme" [5], with decarboxylation, to pyruvate. The NADPH+H formed in this process is also used for fatty acid biosynthesis. 

Eugene Kennedy and Albert Lehninger showed in 1948 that, in eulcaiyotes, the entire set of reactions of the citric acid cycle takes place in mitochondria. Isolated mitochondria were found to contain not only all the enzymes and coenzymes required for the citric acid cycle, but also all the enzymes and proteins necessaiy for the last stage of respiration—electron transfer and ATP synthesis by oxidative phosphoiylation. As we shall see in later chapters, mitochondria also contain the enzymes for the oxidation of fatty acids and some amino acids to acetyl-CoA, and the oxidative degradation of other amino acids to a-ketoglutarate, succinyl-CoA, or oxaloacetate. Thus, in nonphotosynthetic eulcaiyotes, the mitochondrion is the site of most energy-yielding... 

This three-step process for transferring fatty acids into the mitochondrion—esterification to CoA, transesterification to carnitine followed by transport, and transesterification back to CoA—links two separate pools of coenzyme A and of fatty acyl-CoA, one in the cytosol, the other in mitochondria These pools have different functions. Coenzyme A in the mitochondrial matrix is largely used in oxidative degradation of pyruvate, fatty acids, and some amino acids, whereas cytosolic coenzyme A is used in the biosynthesis of fatty acids (see Fig. 21-10). Fatty acyl-CoA in the cytosolic pool can be used for membrane lipid synthesis or can be moved into the mitochondrial matrix for oxidation and ATP production. Conversion to the carnitine ester commits the fatty acyl moiety to the oxidative fate. 

The oxidative phosphorylation system contains over 80 polypeptides. Only 13 of them are encoded by mtDNA, which is contained within mitochondria, and all the other proteins that reside in the mitochondrion are nuclear gene products. Mitochondria depend on nuclear genes for the synthesis and assembly of the enzymes for mtDNA replication, transcription, translation, and repair (Tl). The proteins involved in heme synthesis, substrate oxidation by TCA cycle, degradation of fatty acids by /i-oxidalion, part of the urea cycle, and regulation of apoptosis that occurs in mitochondria are all made by the genes in nuclear DNA. 

On the basis of the pathway of heterophagy (Fig. 1-8), make a proposal for the pathway of autophagic degradation of a mitochondrion. 

Yes, not only is citric acid completely degraded to carbon dioxide and water, but it is also readily absorbed into the mitochondrion. 

The most likely deficiency is a lack of 2,4-dienoyl CoA reductase, an enzyme that is essential for the degradation of unsaturated fatty acids with double bonds at even-numbered carbons. Such fatty acids include linoleate (9-ds,12-ds 18 2). Four rounds of oxidation of linoleoyl CoA generate a 10-carbon acyl CoA that contains a trans-A and a cis-A double bond. This intermediate is a substrate for the reductase, which converts the 2,4-dienoyl CoA to ds-A -enoyl CoA. A dehciency of 2,4-dienoyl reductase leads to an accumulation of trans-A, ds-A -decadienoyl CoA molecules in the mitochondrion. The observation that carnitine derivatives of the 2,4-dienoyl CoA are found in blood and urine provides evidence that these molecules accumulate in the mitochondrion and are then attached to carnitine. Formation of carnitine decadienoate allows the acyl molecules to be transported across the inner mitochondrial membrane into the cytosol, and then into the circulation. 

Figure 1-15 shows the scheme for autophagic degradation of a mitochondrion. Note that once the phagosome has been formed, the process of digestion, etc. is the same as for heterophagy. 

Jakovcic et al. (1971) claimed that the asynchronous increase in activity of the several enzymes does not conflict with the notion that the mitochondrion turns over as a unit. Turnover has usually been studied under steady state conditions of synthesis and degradation, and such conditions may not be applicable diuring periods of rapid growth and differentiation either in fetal cells or in their organelles. Indeed, Neubert et al. (1968) have stated that the faster the growth rate of a tissue, the longer the half-life of mitochondria thus, in a very rapidly growing tissue there is almost no turnover. 

At this point, the activated fatty acid is transported into the mitochondrion, where its carbon chain is degraded by the reactions of j8-oxidation. 

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