- A gene called PHB2 (Prohibitin 2) is expressed in the inner membrane of
the mitochondria, find scientists from the UT Southwestern Medical Centre.
degradation of the mitochondria, the outer membrane is destroyed and PHB2
is present on the surface
- PHB2 binds to the
LC3 receptor present on the surface of autophagosome and leads it to a
lysozyme for natural degradation.
degradation of mitochondria results in the release of reactive oxygen
species that are harmful and lead to cancer, aging and neurodegenerative
- PHB2 could be a potential target for drug therapy in the
treatment of cancer or to reverse certain signs of aging.
mechanism that cells utilize to identify and destroy mitochondria was recently
discovered by a new study from UT Southwestern Medical Center. Mitochondria is
an organelle that is considered to be the powerhouse of the cell, when
this organelle is destroyed, it can lead to numerous diseases that include
, inflammatory disease, cancer
and even aging
Beth Levine, who is the Director of the Centre for Autophagy Research said that
an understanding of how this process works will aid in treating genetic
diseases associated with the loss of mitochondria and also help in reversing
some signs of aging.
The institute is associated with research on autophagy, which is involved in the cells destroying damaged or unnecessary components.
‘Importance of PHB2 gene in mitochondrial degradation would aid in understanding the process better.’
Yongjie Wei, lead co-author, assistant professor of internal medicine said that
mitochondria might be an important organelle that functions by breaking down
sugar to give energy to the cell. However, when this organelle is damaged, it
results in the release of the harmful reactive oxygen species.
is very important for cellular health to remove mitochondria using autophagy
(self-destructive mechanism of the cell). For long, research teams that work on
have always focused on certain protein 'tags' that are present on the surface
of the mitochondria, especially the protein 'Parkin'
that attaches to
these tags. These tags were used to explain the degradation of the organelles
by the cells called autophagosomes, which identify mitochondria that are sick
and signals degradation.
the research team from UT Southwestern University has found that a receptor
that is expressed in the inner membrane of the mitochondria could play a key
role in its degradation.
research team identified a protein called prohibitin 2
(PHB2) present in the inner membrane of the mitochondria, this protein is
expressed when the degradation of the mitochondria results in the outer
membrane being ruptured. The protein LC3 that is present on the surface of the
autophagosomes exterior gets attracted to the prohibitin 2
expressed by the degrading mitochondria.
protein LC3 binds to PHB2 and guides it towards the lysozyme, which is an
organelle with enzymes to digest cellular waste. Dr. Levine adds that the discovery
that the protein PHB2 is essential for mitochondrial degradation is new and
would aid in understanding mitochondria and their degradation process better.
has been previously associated with cancer, aging, neurodegenerative diseases
and inflammation. The association of PHB2 in these diseases aids in
understanding that the mechanism involved in the degradation of mitochondria
plays an important role. An insight into how this process results in disease
progression would help identify new drug targets for treating such diseases.
has also been found to be involved in the degradation of paternal mitochondria,
because only the maternal mitochondria are retained in the developing embryo.
Mitophagy helps in eliminating the paternal mitochondria, and it was first
identified in earthworms. Recent studies, however, have shown that mitophagy
exists in humans too.
Prohibitin 2 in
previous study on prohibitin 2 titled 'Prohibitin-2 promotes hepatocellular
carcinoma malignancy progression in hypoxia based on a label-free quantitative
proteomics strategy' by Cheng J et al showed that prohibitin 2 was involved in
hepatocellular carcinoma. In hepatocellular carcinoma, the rapid growth and
development of the tumor cells lead to a condition
called tumor hypoxia,
a well-known and common feature.
tumor hypoxia leads to a change in the biological properties of tumor cells.
These changes lead to an improvement in cancer survival even under conditions
of stress which make these cells resistant to apoptosis (programmed cell death)
and angiogenesis (development of new blood vessels).
mechanism of action of these malignant hepatocellular cancer cells was not
known earlier. The scientists in the study found that there was a significant
increase in prohibitin 2 in the hepatocellular cancer cells. In the study, the research team of Cheng et
al showed that the treatment of these hepatoma cancer cells, using small
interfering RNAs which were against PHB2, lead to the suppression of the growth
of these cancer cells. Further suppression of PHB2 resulted in the dramatic
repression of the hepatocellular cancer cells to survive in the hypoxic environment.
current study that focuses on the mechanism of mitochondrial degradation
provides insights into many genetic disorders that may be caused by
mitochondria. Though only maternal mitochondria should be present in the
progeny, sometimes, the paternal mitochondria may also be passed onto the
progeny. This leads to a lot of health problems, targeting the PHB2 will aid
in treatment for such genetic disorders
. The Parkin protein has been
studied extensively in autophagy but the research team from UT Southwestern
University has shown that Parkin protein cannot function without PHB2.
could soon be used as a target for drug therapy against many different cancers
as well as in genetic disorders.
- Prohibitin-2 promotes hepatocellular carcinoma malignancy progression in hypoxia based on a label-free quantitative proteomics strategy. - (https://www.ncbi.nlm.nih.gov/pubmed/23661548)