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Mitoptosis, a novel mitochondrial death mechanism leading predominantly to activation of autophagy.

Jangamreddy JR, Los MJ - Hepat Mon (2012)

View Article: PubMed Central - PubMed

Affiliation: Deptartment of Clinical and Experimental Medicine, Integrative Regenerative Medicine Center (IGEN), Division of Cell Biology, Linköping University, Linkoping, Sweden.

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During “outer mitochondrial membrane mitoptosis”, mitochondria undergo condensation, followed by swelling and fragmentation of cristae... During “inner mitochondrial membrane mitoptosis”, the outer mitochondrial membrane remains intact and the cristae deteriorate... We have often observed a third mixed form of mitoptosis in which mitochondria undergo condensation, followed by swelling and vesicular fragmentation of cristae, similar to “outer mitochondrial membrane mitoptosis”, but instead of disruption of the outer mitochondrial membrane, the mitochondria become engulfed in autophagosomes... Thus, the fate of mitochondria inside stressed cells varies, and the study of mitoptosis in different model systems and the subcellular mechanisms underlying these processes still await conclusions... However, the initial apoptotic signal increases mitochondrial membrane potential during the early steps of apoptosis, eventually leading to loss of membrane potential... This initial increase in membrane potential is thought to be due to the ATP dependency of apoptosis, hence, the distantly located mitochondria (resulting from mitochondrial fission or thread-grain transition) need to be transfered to the nuclear surroundings to release apoptotic factors for nuclear transfer; thus, amplifying programmed cell death... The specific removal of dysfunctional or ROS-overproducing mitochondria during apoptosis or mitoptosis is believed to be achieved by autophagy either by autophagosome formation (mitophagy) or by the formation of mitoptotic bodies that are subsequently released into the extracellular environment... The elimination of dysfunctional mitochondria is further supported by studies of cells treated with staurosporin, a common drug used to induce apoptosis, and by the use of pan-caspase inhibitors in which cells survive but lose their mitochondria... More recent studies on PINK1 and Drp1 in neural diseases suggest that dysfunctional mitochondria trigger autophagy and, thus, are eliminated... Thus, suggesting that mitochondrial dysfunction is a good enough reason for eliminating mitochondria and as Dr. Skulachev says, mitochondria follow the samurai’s law; “it’s better to die than to be wrong”.

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Related in: MedlinePlus

Ultrastructural Forms of Mitoptosis.Mitoptosis was induced in PC3 prostate cancer cells Inner Membrane Mitoptosis (A) and in SKBR3 breast cancer cells by overnight treatment with salinomycin. Inner membrane mitoptosis (A) and outer membrane mitoptosis Outer Membrane Mitoptosis (B) in the apoptotic breast cancer cell and prostate cancer cell lines. We have also observed the third type of mitoptosis, which we have coined mitochondrial matrix mitoptosis Mitochondrial matrix Mitoptosis (C) in which both membranes are degraded with the matrix.
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fig43: Ultrastructural Forms of Mitoptosis.Mitoptosis was induced in PC3 prostate cancer cells Inner Membrane Mitoptosis (A) and in SKBR3 breast cancer cells by overnight treatment with salinomycin. Inner membrane mitoptosis (A) and outer membrane mitoptosis Outer Membrane Mitoptosis (B) in the apoptotic breast cancer cell and prostate cancer cell lines. We have also observed the third type of mitoptosis, which we have coined mitochondrial matrix mitoptosis Mitochondrial matrix Mitoptosis (C) in which both membranes are degraded with the matrix.

Mentions: Thus, do mitochondria have the mechanisms to trigger host cell death or is the host directing the mitochondria depending on physiological needs? To what extent are mitochondria autonomous in their function and death? Recent reports about mitochondrial suicide (mitoptosis) and relocation of mitochondria to the nuclear periphery (thread-grain transition) may provide substantial answers to these basic questions. Two very interesting reviews (Skulachev, IUBMB Life 2000, and Skulachev, Apoptosis 2006) by Vladimir P. Skulachev elaborate the fundamental understanding of mitochondrial suicide and the phenomenon of apoptosis and coined the term mitoptosis (17, 18). Mitoptosis takes various forms (Figure 1). Inner membrane mitoptosis may occur, in which only the internal matrix and cristae are degraded while the external mitochondrial envelope remains unaltered, or outer membrane mitoptosis may occur, in which only swollen internal cristae are detected as remnants. Furthermore, the fate of the degraded mitochondria may differ under different experimental conditions. The degraded mitochondria may either become autophagosomes (predominant phenomenon observed in our lab), or mitoptotic bodies, which are extruded from the cell (19).


Mitoptosis, a novel mitochondrial death mechanism leading predominantly to activation of autophagy.

Jangamreddy JR, Los MJ - Hepat Mon (2012)

Ultrastructural Forms of Mitoptosis.Mitoptosis was induced in PC3 prostate cancer cells Inner Membrane Mitoptosis (A) and in SKBR3 breast cancer cells by overnight treatment with salinomycin. Inner membrane mitoptosis (A) and outer membrane mitoptosis Outer Membrane Mitoptosis (B) in the apoptotic breast cancer cell and prostate cancer cell lines. We have also observed the third type of mitoptosis, which we have coined mitochondrial matrix mitoptosis Mitochondrial matrix Mitoptosis (C) in which both membranes are degraded with the matrix.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475017&req=5

fig43: Ultrastructural Forms of Mitoptosis.Mitoptosis was induced in PC3 prostate cancer cells Inner Membrane Mitoptosis (A) and in SKBR3 breast cancer cells by overnight treatment with salinomycin. Inner membrane mitoptosis (A) and outer membrane mitoptosis Outer Membrane Mitoptosis (B) in the apoptotic breast cancer cell and prostate cancer cell lines. We have also observed the third type of mitoptosis, which we have coined mitochondrial matrix mitoptosis Mitochondrial matrix Mitoptosis (C) in which both membranes are degraded with the matrix.
Mentions: Thus, do mitochondria have the mechanisms to trigger host cell death or is the host directing the mitochondria depending on physiological needs? To what extent are mitochondria autonomous in their function and death? Recent reports about mitochondrial suicide (mitoptosis) and relocation of mitochondria to the nuclear periphery (thread-grain transition) may provide substantial answers to these basic questions. Two very interesting reviews (Skulachev, IUBMB Life 2000, and Skulachev, Apoptosis 2006) by Vladimir P. Skulachev elaborate the fundamental understanding of mitochondrial suicide and the phenomenon of apoptosis and coined the term mitoptosis (17, 18). Mitoptosis takes various forms (Figure 1). Inner membrane mitoptosis may occur, in which only the internal matrix and cristae are degraded while the external mitochondrial envelope remains unaltered, or outer membrane mitoptosis may occur, in which only swollen internal cristae are detected as remnants. Furthermore, the fate of the degraded mitochondria may differ under different experimental conditions. The degraded mitochondria may either become autophagosomes (predominant phenomenon observed in our lab), or mitoptotic bodies, which are extruded from the cell (19).

View Article: PubMed Central - PubMed

Affiliation: Deptartment of Clinical and Experimental Medicine, Integrative Regenerative Medicine Center (IGEN), Division of Cell Biology, Linköping University, Linkoping, Sweden.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

During “outer mitochondrial membrane mitoptosis”, mitochondria undergo condensation, followed by swelling and fragmentation of cristae... During “inner mitochondrial membrane mitoptosis”, the outer mitochondrial membrane remains intact and the cristae deteriorate... We have often observed a third mixed form of mitoptosis in which mitochondria undergo condensation, followed by swelling and vesicular fragmentation of cristae, similar to “outer mitochondrial membrane mitoptosis”, but instead of disruption of the outer mitochondrial membrane, the mitochondria become engulfed in autophagosomes... Thus, the fate of mitochondria inside stressed cells varies, and the study of mitoptosis in different model systems and the subcellular mechanisms underlying these processes still await conclusions... However, the initial apoptotic signal increases mitochondrial membrane potential during the early steps of apoptosis, eventually leading to loss of membrane potential... This initial increase in membrane potential is thought to be due to the ATP dependency of apoptosis, hence, the distantly located mitochondria (resulting from mitochondrial fission or thread-grain transition) need to be transfered to the nuclear surroundings to release apoptotic factors for nuclear transfer; thus, amplifying programmed cell death... The specific removal of dysfunctional or ROS-overproducing mitochondria during apoptosis or mitoptosis is believed to be achieved by autophagy either by autophagosome formation (mitophagy) or by the formation of mitoptotic bodies that are subsequently released into the extracellular environment... The elimination of dysfunctional mitochondria is further supported by studies of cells treated with staurosporin, a common drug used to induce apoptosis, and by the use of pan-caspase inhibitors in which cells survive but lose their mitochondria... More recent studies on PINK1 and Drp1 in neural diseases suggest that dysfunctional mitochondria trigger autophagy and, thus, are eliminated... Thus, suggesting that mitochondrial dysfunction is a good enough reason for eliminating mitochondria and as Dr. Skulachev says, mitochondria follow the samurai’s law; “it’s better to die than to be wrong”.

No MeSH data available.


Related in: MedlinePlus