Significance Key members of the Bcl-2 family of proteins that control cell death possess a carboxy-terminal transmembrane segment that contributes to subcellular localization and modulates apoptotic functions. The role of Mcl-1 and specially Bok proteins remains elusive. We reveal that the coexpression of Mcl-1 and Bok TMDs produces an increase in the number of ER mitochondrial-associated membranes (MAMs). Furthermore, our findings provide mechanistic insight into the interaction between Mcl-1 and Bok transmembrane domains that can be envisioned as a target for therapeutic intervention.