Cytochrome c, a protein that belongs to class 1 of the c-type cytochrome family, exerts different functions depending on its cellular localization and the conditions in which it operates; therefore, it can be defined as ‘extreme multifunctional’ protein. It mediates electron-transfer in the respiratory chain and acts as a detoxifying agent to dispose of ROS. In addition, cytochrome c plays a role in cell apoptosis. After its release into the cytosol, the protein binds to APAF-1, activates pro-caspase 9, and triggers an enzymatic cascade leading to cell death. The interaction with cardiolipin, one of the phospholipids making up the mitochondrial membrane, is essential to start apoptosis; the binding partially unfolds cytochrome c, alters the heme pocket region, and facilitates detachment of Met80 from the sixth coordination position of the heme iron. These events change the function of cytochrome c from an electron-transfer shuttle to a peroxidase-like hemoprotein, capable to trigger the process that leads to cell death. This review provides an overview of the key role played by the cytochrome c-cardiolipin interaction in apoptosis. This is not only important per se, it provides interesting perspectives for applications in clinical diagnostics that use the protein as a biomarker.

Santucci, R., Sinibaldi, F., Cozza, P., Polticelli, F., Fiorucci, L. (2019). Cytochrome c: An extreme multifunctional protein with a key role in cell fate. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 136, 1237-1246 [10.1016/j.ijbiomac.2019.06.180].

Cytochrome c: An extreme multifunctional protein with a key role in cell fate

Polticelli F.;
2019-01-01

Abstract

Cytochrome c, a protein that belongs to class 1 of the c-type cytochrome family, exerts different functions depending on its cellular localization and the conditions in which it operates; therefore, it can be defined as ‘extreme multifunctional’ protein. It mediates electron-transfer in the respiratory chain and acts as a detoxifying agent to dispose of ROS. In addition, cytochrome c plays a role in cell apoptosis. After its release into the cytosol, the protein binds to APAF-1, activates pro-caspase 9, and triggers an enzymatic cascade leading to cell death. The interaction with cardiolipin, one of the phospholipids making up the mitochondrial membrane, is essential to start apoptosis; the binding partially unfolds cytochrome c, alters the heme pocket region, and facilitates detachment of Met80 from the sixth coordination position of the heme iron. These events change the function of cytochrome c from an electron-transfer shuttle to a peroxidase-like hemoprotein, capable to trigger the process that leads to cell death. This review provides an overview of the key role played by the cytochrome c-cardiolipin interaction in apoptosis. This is not only important per se, it provides interesting perspectives for applications in clinical diagnostics that use the protein as a biomarker.
2019
Santucci, R., Sinibaldi, F., Cozza, P., Polticelli, F., Fiorucci, L. (2019). Cytochrome c: An extreme multifunctional protein with a key role in cell fate. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 136, 1237-1246 [10.1016/j.ijbiomac.2019.06.180].
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11590/355504
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 136
  • ???jsp.display-item.citation.isi??? 129
social impact