Table 2 Localization and functions of BCL-2 family proteins

BCL-2

Consistently linked to the MOM and/or ER membrane

Both apoptosis effectors and BH3 only proteins are inhibited

[34, 53]

BCL-XL

Located in the nucleus envelope, endoplasmic reticulum (ER), and mitochondrial membrane surfaces

Bind to BAX or BAK to prevent apoptosis

[19, 54]

MCL-1

Placement to the outer mitochondrial membrane (OMM), inner mitochondrial membrane (IMM)

BH3-only proteins are inhibited as well as apoptotic effectors. Has an impact on cellular health and development in addition to its known pro-survival activities

[55]

BCL-W

Loosely connected to the mitochondrial membrane and cytosol

Inhibits BH3-only proteins as well as apoptotic effectors

[19, 34, 36]

A1/Bfl-1

Identified on the Golgi apparatus, cytosol, nuclear envelope, and ER membranes

Opposes the activation of caspase and prevents the release of proapoptotic cytochrome c from mitochondria

[1, 56]

BAK

Always present on the OMM

Oligomerizes to create holes in the OMM, which is considered to enhance MOMP

[57]

BAX

Present on the OMM, often present in the cytoplasm as an inactive monomer

Oligomerizes to create holes in the OMM, which is considered to enhance MOMP

[57]

BOK

Detected on the ER membranes, nuclear outer membrane, and Golgi apparatus

Depends on BAX and BAK to promote apoptosis

[58]

BAD

Both the cytosol and the mitochondrial membrane

BAD is referred to as a "indirect" promoter of apoptosis because it causes cell death through inhibiting antiapoptotic proteins

[59]

BIM

Nucleus envelope, endoplasmic reticulum (ER), cytoplasm, and mitochondrial outer membrane (MOM)

Apoptotic induction, it also controls mitochondrial activity and cellular metabolism

[56, 60]

PUMA

Placement on the mitochondrial outer membrane (MOM)

Crucial p53-dependent apoptosis mediator. Activates BAK and BAX, resulting in MOMP

[19, 61]

BIK

Mostly found in the ER membrane

Directly impacts BCL-2 and BCL-2-like 1

[1, 62]