Mitochondrial autophagy

Teckman, J.H., An, J. K., Blomenkamp, K., Schmidt, B., and Perlmutter, D., 2004, Mitochondrial autophagy and injury in the liver in alpha 1-antitrypsin deficiency, Am. J. Physiol. Gastrointest. Liver... 

Lemasters JJ, Nieminen A-L, Qian T, et al. The mitochondrial permeability transition in cell death a common mechanism in necrosis, apoptosis and autophagy. Biochim Biophys Acta 1998 1366 177-196. 

Lehninger, A.L., 1974, Role of phosphate and other proton-donating anions in respiration-coupled transport of Ca2+ by mitochondria, Proc. Natl. Acad. Sci. USA 71, pp. 1520-1524 Lehninger, A.L., Carafoli, E., and Rossi, C. S., 1967, Energy-linked ion movements in mitochondrial systems, Adv. Enzymol. Relat. Areas. Mol. Biol. 29, pp. 259-320 Lemasters, J.J., Nieminen, A. L., Qian, T., Trost, L., Elmore, S. P., Nishimura, Y., Crowe, R. A., Cascio, W. E., Bradham, C. A., Brenner, D. A., and Herman, B., 1998, The mitochondrial permeability transition in cell death A common mechanism in necrosis, apoptosis and autophagy, Biochim. Biophys. Acta 1366, pp. 177-196... 

An alternative hypothesis is that ER retention of Z-a,-anti trypsin results in autophagy, specifically of hepatic mitochondria. The basis for this hypothesis is the increase in autophagosomes in cells engineered for inducible expression of Z-tx,-antitrypsin. The mutant protein, along with the chaperone molecule calnexin, can be found in these autophagosomes by immune electron microscopy. It is postulated that mitochondrial dysfunction results from the damage to the mitochondria in the PIZZ liver, leading to the hepatic injury. 

MK-2 induced apoptosis to a much lesser extent than GG. The major difference between MK-2 and GG is the u,(J>-unsaluraled ketone structure present in MK-2 but not in GG. The induction of cell death by MK-2 or GG was not coupled with radical generation. It has recently been reported that the induction of apoptosis by MK-4 in human ovary cancer cells is mediated by oxidative stress in mitochondria [70]. Since autophagy plays an important role in reducing mitochondrial damage and reactive oxygen species, there is a possibility that the apoptosis-inducing activity of MK-4 may be derived from the inhibition of autophagy. 

Hamed, H.A., et al. (2010). OSU-03012 enhances Ad.7-induced GBM cell kUhng via ER stress and autophagy and by decreasing expression of mitochondrial protective proteins. Cancer Biol Ther 9 526-536. 

The mitochondrial permeability transition (MPT) is the loss of the inner mitochondrial membrane impermeability to solutes caused by opening of the MPT pore (MPTP). In turn, this action results in a loss of mitochondrial function and provides a common mechanism implicated in activation of mi-tophagy/autophagy, apoptosis, and necrosis in different cell systems. Although the composition of MPTP is not fully settled, multiple studies suggest involvement of adenine nucleotide translocase (ANT) in the inner mitochondrial membrane, voltage-dependent anion channel (VDAC or porin) in the outer membrane, and cyclophilin D (CypD) in the matrix. 

Lemasters JJ, QianT, Elmore SP,Trost LC, Nishimura Y, Herman B, Bradham CA, Brenner DA, and Nieminen AL. Confocal microscopy of the mitochondrial permeability transition in necrotic cell killing, apoptosis and autophagy. BioFactors (Oxford, England) 8 283-285,1998. 

Kessel D, Reiners Jr JJ. Apoptosis and autophagy after mitochondrial or endoplasmic reticulum photodamage. Photochem Photobiol 2004 83 1024. 

Chen Y, Gibson SB. Is mitochondrial generation of reactive oxygen species a trigger for autophagy Autophagy 2008 4 246-248. 

Extensive literature has been dedicated to define the types of cell death, considering morphological and biochemical aspects [86, 87, 88], Induction of death of cancer cells by alterations of mitochondrial bioenergetics have been proposed as promising approach for synthetic and natural compoimd s [23], Mitochondria participate in different types of cellular death, specially apoptosis (intrinsic pathway), programmed necrosis and autophagy [15, 16, 89], which can be triggered by anti-cancer alkaloids. 

Red-Br-nos triggers protective autophagy to the induction of apoptosis and it is an early detectable event that involves double membrane vacuoles, acidic vesicular organelles, increase of expression of LC3-II and beclin-1. This noscapine derivative produces an inerease of ROS levels and induees alterations in mitochondrial architecture, particularly in the intracristal compartment, accompanied of A /m dissipation. ROS production is a key event for autophagy and caspase-independent, ROS-dependent apoptosis induced by Red-Br-nos [116]. 

It increases cytosolic calcium concentration possibly by vanilloid receptor type 1 in endoplasmic reticulum and activates a mitochondrial caspase-dependent death signaling. Moreover, capsaiein induces autophagy with anti-apoptotic effects. Interestingly, inhibition of... 

Fig. 3 Mechanisms of neurodegeneration in PD. Pathogenic mutations may disrupt protein clearance mechanisms (e.g. autophagy) and alter protein expression, causing accumulation of misfolded proteins, such as a-synuclein. Protein aggregates may induce neurodegeneration. Oxidative stress caused by mitochondrial dysfunction may also initiate a cascade of events, including neuroinflammation, leading to neurodegeneration.

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