Posts Tagged: necrosis

Autophagy and Mitophagy in Cardiovascular Disease

Autophagy and Mitophagy in Cardiovascular Disease

José Manuel Bravo-San Pedro, Guido Kroemer, Lorenzo Galluzzi

Detrimental effects of autophagy or mitophagy inhibition on cardiovascular health. Multiple genetic interventions that limit autophagic or mitophagic flux at the whole-body level or in specific compartments of the cardiovascular system have been associated with the spontaneous development of cardiovascular disorders. AP indicates autophagosome; APL, autophagolysosome; Atg5, autophagy related 5; Bnip3l, BCL2 interacting protein 3 like; Dnml1, dynamin 1 like; Fbxo32, F-box protein 32; L, lysosome; Lamp2, lysosomal-associated membrane protein 2; Mfn1, mitofusin 1; Park2, Parkinson disease (autosomal recessive, juvenile) 2, parkin; Pink1, PTEN-induced putative kinase 1; Sirt6, sirtuin 6; Tfrc, transferrin receptor; and Trp53, transformation-related protein 53. [Powerpoint File]

Regulated Necrotic Cell Death: The Passive Aggressive Side of Bax and Bak

Regulated Necrotic Cell Death: The Passive Aggressive Side of Bax and Bak

Jason Karch, Jeffery D. Molkentin

Mitochondrial permeability transition pore (MPTP)-dependent necrotic pathway. When a cell receives a stress that leads to increased levels of intracellular calcium, the mitochondrial calcium uniporter (MCU) takes up the calcium into the matrix of the mitochondria where it can trigger MPTP opening through cyclophilin D (CypD). The MPTP is thought to be composed of the F1F0 ATP synthase regulated by ANT and the mitochondrial phosphate carrier (PiC). On prolonged opening of the MPTP, there is an osmotic alteration and mitochondrial swelling and dysfunction occur with loss of ATP production and reactive oxygen species (ROS) generation. MPTP-dependent mitochondrial dysfunction requires the presence of Bax or Bak on the outer mitochondrial membrane. Therefore, proteins that affect the content of Bax/Bak on the outer mitochondrial membrane, such as the prosurvival the Bcl-2 family members, can secondarily affect MPTP-dependent mitochondrial dysfunction. ANT indicates adenine nucleotide translocator; BH, Bcl-2 homology; IMM, inner mitochondrial membrane; IMS, intramitochondrial membrane space; and OMM, outer mitochondrial membrane. [Powerpoint File]

Regulated Necrotic Cell Death: The Passive Aggressive Side of Bax and Bak

Regulated Necrotic Cell Death: The Passive Aggressive Side of Bax and Bak

Jason Karch, Jeffery D. Molkentin

Necroptotic pathway. The combinatorial treatment with an apoptotic death receptor ligand and a caspase inhibitor leads to necroptosis with receptor-interacting protein kinase 1 (RIP1) activation. Without the caspase inhibitor present, caspase 8 would normally cleave and inactivate RIP1. When RIP1 is left unchecked in the presence of a caspase inhibitor, it complexes with RIP3 and together they lead to the phosphorylation and activation of mixed lineage kinase like (MLKL). MLKL is a required protein for necroptosis. [Powerpoint File]

Regulation of Cell Survival and Death by Pyridine Nucleotides

Regulation of Cell Survival and Death by Pyridine Nucleotides

Shin-ichi Oka, Chiao-Po Hsu, Junichi Sadoshima

Sirt1-mediated protein deacetylation. Sirt1 hydrolyzes NAD+ to generate ADP-ribose units and nicotinamide. The acetyl group of the Sirt1 target proteins is removed and attached to the ADP-ribose to generate 2-O-acetyl-ADP-ribose. [Powerpoint File]