Mitochondrial Dynamics: Functional Link with Apoptosis
Figure 3
Hypothetical models of the role of contacts between mitochondria and ER in apoptosis. The hFis1/Bap31 platform transmits the mitochondrial stress signal to the ER via the activation of procaspase-8. The cytosolic region of the ER integral membrane protein Bap31 is cleaved by activated caspase-8 to generate proapoptotic p20Bap31, which causes rapid transmission of ER calcium signals to the mitochondria via the IP3 receptor. At close ER-mitochondria contact sites, mitochondria takes up calcium into the matrix via the mitochondrial calcium channels MICU1 or LETM1. The massive influx of calcium leads to mitochondrial fission, cristae remodeling, and cytochrome release. Mfn2 is enriched in the mitochondria-associated membranes (MAM) of the endoplasmic reticulum (ER), where it interacts with Mfn1 and Mfn2 on the mitochondria to form interorganellar bridges. Upon apoptosis signal, a BH3-only member of the Bcl-2 family, Bik, induces Ca2+ release from the ER and, in turn, induces Drp1 recruitment to the mitochondria and their fragmentation and cristae remodeling. SERCA, sarco/endoplasmic reticulum Ca2+-ATPase. MICU1, mitochondrial calcium uptake 1. LETM1, leucine zipper/EF hand-containing transmembrane 1.
