Unravel the Mystery of Mitochondria Retrograde Signaling Pathways
Unravel the Mystery of Mitochondria Retrograde Signaling
Pathways
A domestic research team has identified
a key retrograde signaling pathway where mitochondrial dysfunction occurs through
mitochondrial DNA mutation.
Prof. Park, Kyong
Soo, Dept. of Internal Medicine, SNU Hospital, collaborated with Prof. Hwang,
Dae-Hee, POSTECH and Prof. Lee, Bong-Hee and Byun, Kyung-Hee, Gachon University
of Medicine & Science, thereby verifying the role of 'RXRα (retinoid X
receptor alpha)' in the mechanism of mitochondrial dysfunction through mitochondrial
DNA mutation at position 3243 and the recovery of mitochondrial function through
RXRα activation.
This study appeared as the cover paper
in the online edition (Feb. 26) of 'Science Signaling' globally acclaimed as
a leading academic journal.
Mitochondrion is
an organelle that contains its own DNA. As a powerhouse of cells, it plays a
vital role in producing energy for our body.
Reportedly,
mitochondrial dysfunction is highly associated with degenerative diseases like
diabetes, metabolic syndrome, Alzheimer's disease, and Parkinson's disease.
Mitochondrial
DNA mutation at position 3243 is an A to G transition at nucleotide position
3243. It is the most common mutation found in diabetic patients and about 1%
of patients with diabetes in Korea has this mutation. But, it is unclear how
this mutation leads to mitochondrial dysfunction and subsequent development
of diabetes mellitus.
The research team generated cybrid
cells carrying different degree of this mutation by fusing cells carrying no
mitochondrial DNA but a nucleus with patient’s platelets harboring mutated
mitochondrial DNA, and analyzed gene expression profiles in these cybrid cells.
With
a substantial decrease in the expression and function of mitochondrial protein,
RXRα proved to be a vital transcription factor behind such phenomenon.
In
the fusion cell with mitochondrial DNA mutation at position 3243, RXRα declined
by 50%~75% due to a rise in reactive oxygen. This decreased the expression of
mitochondrial protein as mitochondrial functions dropped by 45%~65%.
Here,
RXRα activation increased the interaction between RXRα and another transcription
factor PGC1α, which resulted in the recovery of about 40% of mitochondrial
functions.
“This study has crucial implications for
raising the possibility for the first time that RXRα is a major target of therapy
for mitochondrial dysfunction caused by mitochondrial DNA mutation. I expect
further in-depth studies can pave the way for the treatment of degenerative
diseases due to mitochondrial dysfunction,” told Prof. Park, Kyong Soo.