Cytochrome c and insect cell apoptosis

The role of cytochrome c in insect cell apoptosis has drawn considerable attention and has been subject to considerable controversy. In Drosophila, the majority of studies have demonstrated that cytochrome c may not be involved in apoptosis, although there are conflicting reports. Cytochrome c is not released from mitochondria into the cytosol and activation of the initiator caspase Dronc or effector caspase Drice is not associated with cytochrome c during apoptosis in Drosophila SL2 cells or BG2 cells. Cytochrome c failed to induce caspase activation and promote caspase activation in Drosophila cell lysates, but remarkably caused caspase activation in extracts from human cells. Knockdown of cytochrome c does not protect cells from apoptosis and over-expression of cytochrome c also does not promote apoptosis. Structural analysis has revealed that cytochrome c is not required for Dapaf-1 complex assembly. In Lepidoptera, the involvement of cytochrome c in apoptosis has been demonstrated by the accumulating evidence. Cytochrome c release from mitochondria into cytosol has been observed in different cell lines such as Spodoptera frugiperda Sf9, Spodoptera litura Sl-I and Lymantria dispar LdFB. Silencing of cytochrome c expression significantly affected apoptosis and activation of caspase and the addition of cytochrome c to cell-free extracts results in caspase activation, suggesting the activation of caspase is dependent on cytochrome c. Although Apaf-1 has not been identified in Lepidoptera, the inhibitor of apoptosome formation can inhibit apoptosis and caspase activation. Cytochrome c may be exclusively required for Lepidoptera apoptosis.