Study Provides More Evidence for a Central Role of
Mitochondria in Apoptosis
PA) - Within the workings of a human cell there is an
innate mechanism for self-destruction - a carefully
choreographed act called apoptosis, or programmed cell
death. Without apoptosis, diseased cells, especially
cancerous cells, are not eliminated from the body and
can continue to threaten other cells. Not surprisingly,
cancer researchers are trying to piece together the
mechanics of apoptosis and how they can use it against
In the June 15 issue of Genes and Development, researchers
from the University of Pennsylvania School of Medicine
identify the essential role of two pro-apoptotic proteins,
Bax and Bak, in initiating apoptosis.
This new work demonstrates that cells lacking Bax and
Bak cannot be killed by either chemotherapy or irradiation.
It also demonstrates conclusively what scientists have
suspected for several years: that chemotherapy and irradiation
work to treat cancer by tricking the cancer cell into
committing suicide. This study is the third of a series
of articles that researchers have published in recent
months exploring the functional role of the Bcl-2 family
of proteins - of which Bax and Bak are members - in
regulating cell death.
"Within the Bcl-2 family of proteins, some proteins
are actively pro-apoptotic while others are anti-apoptotic,"
said Craig B. Thompson, M.D., scientific director of
the Abramson Family Cancer Research Institute at the
Penn Cancer Center. "The result is a careful balance
where one set of the proteins prevents the other from
In this new report Thompson and his colleagues demonstrate
that this balancing act takes place on the surface of
a cell's mitochondrion, which is the cellular organ
devoted to converting sugars and fats into usable energy
for the cell. In cells that lack Bak and Bax, the researchers
demonstrate that virtually all forms of cell death are
eliminated. Without Bax or Bak to turn off the function
of the mitochondria, cells become immortal.
"Although we have known that damaged mitochondria
can initiate apoptosis, the importance of mitochondria
in this process has become a central issue," said
Thompson. "We believe the new evidence demonstrates
that the mitochondria plays a major role in all forms
of apoptosis. This has important implications for the
development of new cancer treatments as well as provides
new hope that cell death can be prevented during a stroke
or heart attack."
It is Bax and Bak, however, that are essential in carrying
out the disruption of mitochondria. Interestingly, Bax
and Bak are also redundant, as either protein - by itself
- is effective in triggering apoptosis. According to
Thompson, the redundant role of Bax and Bak represents
a previously unknown but essential step in regulating
apoptosis. "The fact that we have two separate
proteins that do the same essential job stresses the
importance of this step in controlling cell survival,"
Bax and Bak also illustrate the overall complexity of
the mechanism behind apoptosis. But by examining how
individual parts of the mechanism function, the researchers
hope to map out new ways to correct for the mechanism
when it fails.
"To look at it broadly, there are only two major
types of diseases: ones where cells are killed and ones
where cells refuse to die," said Thompson. "Cancer
is one of the latter - it occurs when diseased cells
that do not respond to apoptotic signals grow out of
control. The trick is to find a way to get cancer cells
to respond to those signals."
Contributors to this research include Wei-Xing Zong,
PhD, and Tullia Lindsten, PhD, of the Abramson Family
Cancer Research Institute at Penn and Andrea J. Ross,
PhD. and Grant R. MacGregor, PhD., of the Center for
Molecular Medicine at the Emory University of School
Their research has been funded by the National Institutes
of Health and The Leonard and Madlyn Abramson Family
Cancer Research Institute at the University of Pennsylvania
# # #
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $6.7 billion enterprise.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.