The multiple functions of cytochrome c and their regulation in life and death decisions of the mammalian cell: From respiration to apoptosis

Abstract

Cytochrome c (Cytc) is essential in mitochondrial electron transport and intrinsic type II apoptosis. Mammalian Cytc also scavenges reactive oxygen species (ROS) under healthy conditions, produces ROS with the co-factor p66 Shc , and oxidizes cardiolipin during apoptosis. The recent finding that Cytc is phosphorylated in vivo underpins a model for the pivotal role of Cytc regulation in making life and death decisions. An apoptotic sequence of events is proposed involving changes in Cytc phosphorylation, increased ROS via increased mitochondrial membrane potentials or the p66 Shc pathway, the oxidation of cardiolipin by Cytc, and its release from the mitochondria. Cytc regulation in respiration and cell death is discussed in a human disease context including neurodegenerative and cardiovascular diseases, cancer, and sepsis.

Potential threat of Chlorpyrifos to human liver cells via the caspase-dependent mitochondrial pathways

“…The two most important characteristics of the mitochondrial-mediated apoptotic pathway are loss of MMP and release of cytochrome c (Garrido et al, 2006). The disruption of MMP is an important means of turning on/off apoptosis and it is recognized as the key step in the apoptotic cascade (Hüttemann et al, 2011). The results of the fluorescence microscopy experiments show CPF can induce the disruption of MMP in a concentration-dependent manner (Figure 3(B)).…”

Fisetin, a dietary flavonoid induces apoptosis via modulating the MAPK and PI3K/Akt signalling pathways in human osteosarcoma (U-2 OS) cells

“…Bcl-2 family proteins are involved in the regulation of apoptosis and mitochondrial membrane potential (Hunter et al, 2007;Heath-Engel et al, 2008;GyrdHansen and Meier, 2010;Huttemann et al, 2011). The pro-apoptotic Bcl-2-family proteins such as Bax and Bak form pores in the outer mitochondrial membrane and stimulate apoptosis, while the anti-apoptotic proteins including Bcl-2 and Bcl-xL inhibit pore formation (Gross et al, 1999).…”

Effects of intrinsic aerobic capacity, aging and voluntary running on skeletal muscle sirtuins and heat shock proteins

“…Besides UCPs, also amount and efficiency of mitochondria to produce 99 heat affects body temperature. PGC-1 plays a key role in mitochondrial biogenesis whereas 100 cytochrome c (cyt c) is a crucial component of the electron transport chain in mitochondria 101 and hence these proteins are essential for muscle oxidative capacity (Huttemann et al 2011, 102 Lin et al 2015. Endurance exercise is known to increase PGC-1 levels and mitochondrial 103 biogenesis in muscle, although UCP levels are found to be reduced , 104 Freyssenet, Berthon & Denis 1996, Holloszy 2008, Nozu et al 1992, Pilegaard et al 2000, 105 Russell et al 2003.…”