1,721,151 research outputs found
Cristae Remodeling and Mitochondrial Fragmentation: A Checkpoint for Cytochrome c Release and Apoptosis?
No full textA crucial amplificatory event in several apoptotic cascades is the complete release of cytochrome c from mitochondria. This is accomplished by the activation of multidomain proapoptotic members of the Bcl-2 family and accompanied by changes in the internal structure of mitochondria, a process known as cristae remodelling, and by mitochondrial fragmentation. Here we illustrate the role of dynamin-related proteins controlling mitochondrial morphology in the regulation of cristae remodelling, organelle fragmentation, cytochrome c release, apoptosis and genetic diseases like dominant optic atrophy; and discuss the controversies on their functional role in apoptosis, with an outlook on the possible exploitation of the inhibition of these proteins in cancer chemotherapy
Mitochondrial Apoptosis Regulation by Bcl-2 Family Members
No full textA key ampLificatory mechanism of programmed cell death depends on the release of proapoptotic factors from the mitochondria, crucial organelles in intermediary metaboLism, and energy conversion characterized by a dynamic morphology, ultrastructure, and intracellular locaLization. The proapoptotic factor required for the assembly of the apoptosome and hence for the activation of effector caspases is the only soluble component of the mitochondrial electron transport chain, cytochrome c, whose submitochondrial locaLization is controlled by the organellar shape. Its release across the outer mitochondrial membrane is controlled by the cell death regulator proteins that belong to the family of B cell lymphoma (BCL)-2, the first oncogene to be discovered to function in the regulation of apoptosis. In this article, we will summarize how Bcl-2 family members recruit mitochondria in the apoptotic pathway, by causing their permeabiLization and morphological remodeLing
Sweetening mitochondria: Hexokinase shields mitochondria from fission when glucose is low
No full textIn this issue of Molecular Cell, Pilic et al.1 show that hexokinase, the first enzyme of glycolysis, forms perimitochondrial rings that prevent mitochondrial fragmentation when ATP levels drop
The mitochondrial pathway: Focus on shape changes
No full textMitochondria are key participants in cell death. They amplify death signals by releasing proapoptotic proteins normally stored in their intermembrane space, such as cytochrome c. In recent years, cytochrome c release has been demonstrated to be not only highly regulated by the proteins of the Bcl-2 family, but also influenced by changes in mitochondrial shape, including remodeling of the cristae and fragmentation of the cytosolic network, both orchestrated by a large group of mitochondria-shaping proteins. We focus our attention in this chapter on the involvement of mitochondrial shape changes in apoptosis and on their regulatory mechanisms. In particular, we discuss the roles of the pro-fusion OPA1 protein and of the inner mitochondrial membrane rhomboid PARL on cristae remodeling and apoptosis in mammals, and on the relationship among Bcl-2 family members, mitochondrial fragmentation, and cell death. These results open the possibility to modulate mitochondrial morphological changes in order to influence apoptosis and thus to intervene in the natural history of human diseases, from neurodegeneration to cancer
Mitochondrial dynamics: roles in exercise physiology and muscle mass regulation
No full textHow mitochondria alter their morphology to meet cellular demands epitomizes the ‘form follows function’ architectural principle. These remodeling events are collectively termed ‘mitochondrial dynamics’. The influence of mitochondrial dynamics and of the mitochondria-shaping proteins that control it on skeletal muscle physiology has become clearer. Endurance exercise prompts mitochondrial morphological changes that augment the respiratory capacity of the worked muscles. Mechanistically, exercise training increases mitochondrial fusion protein levels in skeletal muscle to promote the development of a hyperfused mitochondrial network that possesses denser cristae. Conversely, disruptions to the mitochondrial network through imbalances in mitochondrial dynamics lead to muscle atrophy. Insight into the connection between mitochondrial morphology and muscle-mass maintenance will help to pinpoint therapeutic targets that can be exploited to counteract sarcopenia and muscle atrophy in patholog..
- …
