00:00Mitochondrial function down. So, two things. We can improve the mitochondrial health by increasing more activity. And also, while increasing more activity, we can fight the aging.
00:14So, also, there are genetic mutations in the mitochondrial genome, which we cannot fight back anyway. And there are infections, some bacterias, viruses, they definitely affect the mitochondrial health.
00:30So, there are some signaling pathways, which are normally affecting the, they are actually playing with the mitochondria. You can say, first of all, energy sensing mechanisms, which are very important, like the MPK. CERB is one of the very important.
00:48So, when we talk about certain, I chose to talk about the NOX. So, when, you can say, whenever this cyclic GMP is activated, either by itself or by nitric oxide, it can activate BGC-alpha.
01:18And BGC-alpha will activate the NRF1, which is actually the enzyme which can trigger the mitochondrial proliferation. So, there are different factors in the mitochondrial proliferation. So, mostly, they are activated by different stimuli.
01:37So, inflammation, any kind of inflammation can affect the mitochondria in the cell. So, this, this diagram will tell you, you can see inflammation and this whole mechanism on the top. You can say, once the, once the inflammation happens, it can activate the, through, through ROS production, the ROS production can, can damage the mitochondria, which can damage mitochondria,
02:04can split into separate parts of the mitochondria. And, to cope up this, because when we have a high ROS, then there is ATP deprivation. The ATP will go down. So, it means mitochondria function will disturb.
02:16So, to cope up this mechanism. So, to cope up this mechanism, the CRE, the CRE, you know, the pathways activate, which, which sends, which reduces more energy, and which starts the mitochondrial prologenesis.
02:28When mitochondria start regrowing, it can counter the anti-inflammation mechanism, and block the mechanism, block the inflammation in the cells.
02:40So, normally, in the, as I talked, many bacterias and pathogens can affect the mitochondrial health. So, this is the first, it's a general mechanism. So, we can say it's, sorry, it's about,
02:54NF Kappa B, NF Kappa B, can activate the ROS, and ROS can damage the mitochondria, and also, like, in response, when energy privilege will happen.
03:06So, the athletic mechanism, by NRF2, will increase the mitochondrial biogenesis in this way. So, mitochondria will grow more, and they'll fight back the, the, the pathogenesis of,
03:18uh, uh, bacterias, or whatever, and also inflammation. So, it's, it's a, it's a short example where you can see a lot of bacteria, viruses,
03:26they, they, they, they actually deplete the mitochondria, they, they break down the mitochondria. So, this is, uh, still, uh, in a lot of,
03:34we are, we're trying to fight with a lot of viruses, a lot of bacterias, uh, through killing them, but, uh, sometimes we don't know, they're, they're damaging our,
03:43we're inside ourselves. So, uh, normally, disease is associated with, uh, mitochondria as a number of diseases, you can say,
03:52but, uh, one of the diseases, uh, uh, is a cardiac, cardiac disease is one of the, one of the main, so that's why I, I would say,
03:59maybe I'll talk more about the cardiac disease today. So, uh, other diseases included, you can say, autism,
04:04rural disorders, development disorders, so, uh, which, uh, maybe I don't talk about them more, so that's why.
04:10The cardiac disease is the one of the key factors, the key disease is getting better than mitochondria.
04:16So, how we diagnose, if, if it is a, is it a mitochondrial disorder or is it a general disorder?
04:23So, it is, uh, we would say, so normally it's difficult to diagnose. So, if it is diagnosed, it's, uh, maybe misdiagnosed.
04:32So, if we say, uh, one in two, four thousand plus, uh, you can say individuals in the United States,
04:40they have mitochondrial disorders. And, uh, it is estimated that one, every 30 minutes child born,
04:48will have a mitochondrial disease, disease by one 10 year old. When he, when he gets a 10 year old,
04:54he may have a mitochondrial disease. This is the prediction. This is the estimated, uh, rate.
04:58So, normally the genetic, uh, testing is performed for the mitochondrial genome,
05:03to see if there is any mitochondrial genome effect, nutrition or something.
05:07Also, some there are biochemical tests. But, after all, this area of science is,
05:12is not really studied. So, they're not, we don't have much knowledge about it.
05:16So, that's why we don't know a lot of, uh, uh, a lot of genes, uh, studies.
05:22So, we don't know the, uh, uh, the matter with the genes associated with mitochondrial disorders.
05:28So, it's a little bit away from the mitochondria, mitochondrial topic.
05:34But, I don't know why I included it. I will, I will explain.
05:37It's about a congenital heart disorder. Like, uh, you can say prenatal, uh, genetic testing.
05:43So, uh, it's, we did some study on, uh, on, uh, almost more than, more than 100 patients.
05:50Uh, uh, we, we identified them using, uh, ultrasound and, uh, ECG.
05:55We found they have some cardiac problem. And, uh, we find that, uh, more than 20% of the patients,
06:01they are diagnosed with, uh, different genetic, uh, mutations, uh, CNVs, uh, different CNVs.
06:08And, uh, we find that, uh, the patient with a complex, uh, congenital, congenital heart disorder
06:15has more, uh, uh, mutations than the, than the, than the isolated, uh, CHDs.
06:24So, here, uh, to show this one, uh, actual, like, only view.
06:29The more important thing, it's, we, you know, we say that patients, in the future,
06:35they have a cardiac arrest, or maybe they have a cardiac disorder.
06:38We talk about, we blame many other things.
06:40But, normally, we don't blame the genome.
06:42So, we don't, we don't talk about the genome. We talk about other factors.
06:46Okay, maybe, uh, there are, uh, high cholesterol level.
06:51But, we don't, maybe, we don't talk about the genome.
06:53Maybe something hidden inside the genome, which is causing the cardiac, cardiac disease.
06:58So, here, we identified, uh, some, uh, solutions.
07:04You can say, chromosomal aberrations, which, uh, on the genes, on the chromosomes,
07:09that, uh, can, could be associated with, uh, cardiac diseases.
07:13So, uh, to further figure out, to further figure out, I, we isolated these, uh, these, uh, top regions,
07:22which have a situation with, uh, with the cardiac diseases.
07:25So, we, we added, uh, genes.
07:26So, these genes, what you can say, in, uh, sorry.
07:28So, these genes.
07:29Yeah, these genes, you can see, uh, almost, uh, 20 of them there.
07:30They, they never been recorded with any cardiac disorder.
07:31So, and two, two of them, like, uh, the grade one, and, uh, like, uh, the other gene, uh, MYH11.
07:34These genes have some role in, uh, in cardiac diseases.
07:54So, we, it's this area of research is still untouched.
07:59We study other factors, but we totally neglected that something in the genome.
08:06But, this is still there, but we, why I show here, my topic of talk is mitochondria.
08:13Because we don't study mitochondrial genomes, we had no studies on mitochondrial genomes.
08:19In CHDs or HDs, we don't have any mitochondrial studies.
08:24And normally, we don't do the neonatal diagnosis or prenatal diagnosis for the cardiac disorders in the neonatal.
08:35So, we need to focus on this area of research, which can definitely prevent the future chances of developing cardiac disorder.
08:46So, how the mitochondria has to play a role, have to play a role in the cardiac disease.
08:56So, as this figure, as you can see, when there is a lack of oxygen,
09:02lack of oxygen will trigger the anaerobic glycolysis.
09:07Because the anaerobic glycolysis will create the pyrowake and also suddenly shut down of pH.
09:16Which automatically will cause the cardiomyocyte's death.
09:21So, which will definitely prevent the cardiomyocyte's death, may lead to the cardiac arrest.
09:26So, to cover up this one, supplementing the oxygen can help, supplementing the nutrition can help.
09:33So, but, when we provide a lot of oxygen, sometimes, you know, we need to control that dose.
09:41So, it can increase the ROS, and increase the ROS can damage the cell as well.
09:46But, when the cell is dead, it means it's a problem for the overall heart.
09:56So, that's why the mitochondria is very important.
09:59Here we see a lot of cell death mechanisms, which are associated with the mitochondria.
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