Mitophagy and Mitoptosis in Disease Processes - Protein Misfolding and Cellular Stress in Disease and Aging - page 100

Fig. 2. Scheme illustrating different scenarios of mitochondrial elimination. See text for more details. Abbreviations ATP,
adenosine-5 ¢ -triphosphate; MPT, mitochondrial permeability transition; ROS, reactive oxygen species.

of mitochondrial clusters by a membrane and formation of a
mitoptotic body, (4) decomposition of mitochondria inside the
mitoptotic body to small membrane vesicles, (5) protrusion of
the mitoptotic body from the cell inside a bleb and its subsequent
release into the extracellular space ( 63 ) (Fig. 2 ).

6.2. Mitoptosis
in Disease Processes:
An Immunogenic
Role?

Understanding the role of mitoptosis in pathogenic mechanisms
of mitochondria-associated human diseases is far from being fully
elucidated (Fig. 1 ). However, recently, a connection between
mitochondria, cell death (perhaps by mitoptosis) and B cell toler-
ance has been drawn ( 64 ). It has been hypothesised that the pres-
ence of circulating autoantibodies against mitochondria can be a
marker of autoimmune disease as well as a pathogenic determi-
nant ( 57, 63, 64 ). Clearly release of mitochondrial material into
extracellular compartments arising from mitoptosis could con-
tribute to the production of such autoantibodies. Furthermore,
in many cases, death of autoreactive B cells is regulated by the cell
intrinsic, or mitochondrial pathway of apoptotic cell death. The
pro-apoptotic Bcl-2 family proteins (e.g. Bak, Bax, and Bim) are
required, whereas the anti-apoptotic members (e.g. Bcl-2, Bcl-xL)
can prevent apoptotic cell death by interfering with the action of
Bak and Bax. Notably, Bcl-2 and Bcl-xL have also been shown to
regulate autophagic cell death that may also play a role in B cell
tolerance ( 64 ).