Fig. 3.

Mechanisms of cytochrome c release in mitochondria under heat stress conditions. Increase in cytosolic Ca²⁺ can cause Ca²⁺ influx into the mitochondria through the outer and inner mitochondrial membranes, with the involvement of voltage-dependent anion channels (VDAC) and of the mitochondrial calcium uniporter (MCU) (Li et al., 2013; Rikhvanov et al., 2014; Wagner et al., 2015, 2016). Ca²⁺ influx into the matrix can lead to dissipation of the transmembrane potential and ROS production, thus enabling the formation of permeability transition pores (PTP) and cytochrome c release (Gao et al., 2008; Vianello et al., 2012; Zancani et al., 2015). Cytochrome c release involves mechanisms of destabilization of cytochrome c–cardiolipin interactions (Vacca et al., 2006; Pineau et al., 2013; De Paepe et al., 2014). In the cytosol, cytochrome c interactions can affect nucleic acid and protein dynamics, carbon metabolism and regulation of programmed cell death (Martínez-Fábregas et al., 2013). Blue and red arrows respectively indicate mitochondrial and cytochrome c-dependent processes. Δψ, transmembrane potential; eIF, translation initiation factor; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; NRP, nucleosome assembly protein-related protein; TCL, transcriptional coactivator-like.