The mitochondrial protein apoptosis-inducing factor (AIF) plays a pivotal role in poly(ADP-ribose) polymerase-1 (PARP-1)-mediated cell death (parthanatos), during which it is released from the mitochondria and translocates to the nucleus. We show that AIF is a high-affinity poly(ADP-ribose) (PAR)-binding protein and that PAR binding to AIF is required for parthanatos both in vitro and in vivo. ...

OBJECTIVES The purpose of this study was to identify apoptosis-inducing factor (AIF) as a cardiac mitochondrial antioxidant and assess the efficacy of EUK-8, a salen-manganese catalytic free radical scavenger, to protect the AIF-deficient myocardium against pressure overload. BACKGROUND Oxidative stress has been postulated to provoke cell death and pathologic remodeling in heart failure. We rec...

According to current understanding, cytoplasmic events including activation of protease cascades and mitochondrial permeability transition (PT) participate in the control of nuclear apoptosis. However, the relationship between protease activation and PT has remained elusive. When apoptosis is induced by cross-linking of the Fas/APO-1/CD95 receptor, activation of interleukin-1beta converting enz...

Apoptosis-inducing factor (AIF) and AIF-homologous mitochondrion-associated inducer of death (AMID) are both mitochondrial flavoproteins that trigger caspase-independent apoptosis. Phylogenetic analysis suggests that these two proteins evolutionarily diverge back from their common prokaryote ancestor. Compared with AIF, the proapoptotic nature of AMID and its mode of action are much less clarif...

BACKGROUND/AIMS A(3) adenosine receptor mediates apoptosis in a variety of cancer cells via diverse signaling pathways. The present study was conducted to assess A(3) adenosine receptor-mediated apoptosis in human bladder cancer cell lines and to understand the underlying mechanism. METHODS Human bladder cancer cell lines such as 253J, 5637, KK-47, TCCSUP, T24, and UMUC-3 cells were cultured....

We describe the association of caspase-dependent and caspase-independent mechanisms in macrophage apoptosis induced by LpqH, a 19 kDa Mycobacterium tuberculosis lipoprotein. LpqH triggered TLR2 activation, with upregulation of death receptors and ligands, which was followed by a death receptor signaling cascade with activation of initiator caspase 8 and executioner caspase 3. In this caspase-me...

Nephrotic-range proteinuria is due to glomerular diseases characterized by podocyte injury. Glucocorticoids are the standard of care for most forms of nephrotic syndrome. However, the precise mechanisms underlying the beneficial effects of glucocorticoids on podocytes, beyond its general immunosuppressive and anti-inflammatory effects, are still unknown. This study tested the hypothesis that th...

McMillan EM, Quadrilatero J. Differential apoptosis-related protein expression, mitochondrial properties, proteolytic enzyme activity, and DNA fragmentation between skeletal muscles. Am J Physiol Regul Integr Comp Physiol 300: R531–R543, 2011. First published December 9, 2010; doi:10.1152/ajpregu.00488.2010.—Increased skeletal muscle apoptosis has been associated with a number of conditions inc...

LIST OF ABBREVIATIONS: AIF, apoptosis inducing factor; CcO, cytochrome c oxidase; • • m, mitochondrial membrane potential; ER, endoplasmic reticulum; EM, electron microscopy; IMM, inner mitochondrial membrane; jp, jimpy mouse; mtCK, mitochondrial creatine kinase; Olg, oligodendrocyte; OMM, outer mitochondrial membrane; PARP, poly (ADP-ribose) polymerase; Plp1, X-linked myelin proteolipid protei...

OBJECTIVES The purpose of this study was to identify apoptosis-inducing factor (AIF) as a cardiac mitochondrial antioxidant and assess the efficacy of EUK-8, a salen-manganese catalytic free radical scavenger, to protect the AIF-deficient myocardium against pressure overload. BACKGROUND Oxidative stress has been postulated to provoke cell death and pathologic remodeling in heart failure. We r...