POD: A New Mechanism of Autophagy in Mitochondria

[@Physionic]

If you made it to the end, congratulations - that was a marathon. Hopefully you picked up some interesting information.

[@thewrightoknow]

am in the process using a process of trying to reverse my Type 2 Diabetes buy fasting with water only for 72 hours a week for three to four months to dump all the glucose of my cells. Any thoughts on this? Thanks

[@barbararupp6602]

Xzaasx, and. No , free we see re r4 by, hubby I never hi BB bb 😅 in

[@kentauree]

Please make a video telling people how SSRIs will damage your mitochondria. I have been extremely tired and sick since I took SSRIs 13 years ago. It's not medicine its extremely dangerous poison. Big pharma is selling this because they want you to be sick, because then you buy more medicine (poison)

[@thomasskokan2001]

@@thewrightoknow How are you doing ? I am nearing my 5 yr anniversary in 3 mons. Reversed my type II in 40 days following a 5 day hospitalization ( 1st time in 47yrs ) & a toe amputation .....They gave me insulin in hospital , but I got off it immediately upon discharge....They put me on Metformin, but it made me sick & messed up my bowels so I weaned off it in 3 weeks....Did a 10 day water only fast as soon as I got home.Have lost , 70 lbs & kept 60 of it off 5 yrs later l. Still experimenting with various diets but INTERMITTENT FASTING REMAINS THE BEDROCK of my beating type II.When you do eat ....EAT YOUR FOOD , DON'T DRINK IT ‼️ Drink WATER 🌊💦🌊💦💦🌊💦🌊💦 EAT FOOD ....REAL FOOD ...NOT OVERPROCESSED CRAP.Avid sugar & fake sweeteners / MSG ( Excitotoxins) / fake "meat" / snacks / KEEP IT SIMPLE ‼️ ‼️

[@whitehorse1959]

Yesterday I visited a microbiologist. He was much bigger than I expected.

[@antonanon]

Congratulation on the publication of your paper! Thank you for sharing your deep understanding of molecular biology & stimulating my own interest in this fascinating field. Thank you also for not patronising your lay audience.

[@rickyteee]

I feel I’m getting g a free advanced education from your videos

[@Physionic]

You are, haha. I'm glad to have you, though, ricky.

[@wilmerwalton5089]

I'm motivated to understand how things work generally, as well as how things work for me. Given that autophagy is beneficial in the aging process, I'm interesting in encouraging autophagy. In the standard pathway it's encouraged by fasting and exercise. Assuming the research isn't in on how to encourage this new pathway, except through extremely invasive methods, would you care to speculate on how this new pathway can be encouraged through "natural" methods like diet and exercise?

[@Physionic]

I doubt this new method could be stimulated, because its dependent on the condition that Parkin is not present. I'd venture to say that if anything, people would want to still focus on the classical pathway.

[@wilmerwalton5089]

@@Physionic Thanks, I'll keep on keeping-on. Thanks for not dumbing down the material so much it didn't serve as an introduction to the paper.

[@ResidualSelfImage]

Just learnt about mitophagy this year -thanks for the video

[@Vogeln]

Wow! BRAVO. Another fabulous video!!! As an amateur/hobbyist, I can't claim that I understood everything but the little bit that I DID understand elicited almost as many questions that new knowledge your video imparted. In the interest of brevity, here's just one. You mentioned that under certain conditions, two (or perhaps more) mitochondria fuse and, under other conditions, they fissure. With that in mind, what happens to the mitochondrial DNA? Are mitochondrial DNA expressed throughout its lifetime or are they vestigial, non-encoding DNA? Is this the reason why either halving or doubling of the mitochondrial DNA is not harmful to the mitochondrion or....do mitochondria undergo mitosis/meiosis when they fissure/join?

[@Physionic]

Great question, J. Mitochondrial DNA is reproduced when undergoing fission. During fusion, mitochondrial DNA is simply incorporated with the already present DNA of the host mitochondrion.

[@Vogeln]

@@Physionic Thank you!

[@Rocky7729]

Thanks for explaining the classical understanding of mitophagy. Even after studying in the medical school, this concept was unclear. Appreciate your efforts!

[@jonnyde]

🎯 Key Takeaways for quick navigation: 00:00 🔬 Introduction to the Podcast and Research - Introduction to the podcast and the research topic focused on autophagy and mitochondria. - Mention of the research paper titled "Parkin independent mitophagy via drp1 mediated outer membrane severing and inner membrane ubiquitination." - Overview of the significance of mitochondria in cellular processes. 05:17 🔍 Functions and Regulation of Mitochondria - Explanation of the functions of mitochondria, including energy production. - Briefly mentioning cellular health and survival mechanisms related to mitochondria. - Introduction to the two catabolic systems: proteasome and autophagy. 11:44 🔄 Autophagy and Mitophagy - Distinction between autophagy and mitophagy. - Explanation of the traditional parkin-pink pathway in mitophagy. - Discussion of the ubiquitination process and how it tags proteins on the outer mitochondrial membrane. 19:34 ⚙️ Autophagy Process Overview - Explanation of how autophagy is initiated when ubiquitin-tagged proteins accumulate on the outer mitochondrial membrane. - Introduction to adapter proteins and their role in autophagy. - Formation of the phagosome and engulfment of the damaged mitochondrion. 24:09 🔬 Mitochondrial Structure and Localization of Proteins - Mitochondria have cristae, folding structures that increase surface area for energy production. - Proteins like TOM and CLPP are located in different mitochondrial compartments. - Localization of proteins is important for research on mitochondria. 27:12 🧪 Effects of Actinin on Mitochondria - Actinin is used to induce protein toxicity in mitochondria. - Actinin disrupts mitochondrial protein synthesis, leading to non-functional proteins. - Some mitochondria accumulate cytochrome c while others lose it in the presence of actinin. 34:05 🔗 Role of DRP1 in Mitochondrial Fission - DRP1 is essential for mitochondrial fission, the process of mitochondria splitting into two. - Cells with DRP1 knockout elongate mitochondria instead of separating them. - Actinin's effect on cytochrome c depends on mitochondrial fission. 37:44 💊 Comparison of Different Drugs' Effects - Actinin specifically induces mitochondrial protein toxicity, unlike other drugs. - Chloramphenicol blocks protein synthesis and reduces actinin's effect. - Actinin-induced protein toxicity is the key factor in mitochondrial changes. 39:35 🧬 Protein Toxicity and Ubiquitination - Actinin-induced protein toxicity leads to mitochondrial mosaicism, varying cytochrome c levels. - Only protein toxicity causes mitochondrial changes, not general stress. - Chloramphenicol reduces actinin's effect, linking it to protein toxicity. 43:05 🔬 Super Resolution Imaging of Mitochondria - Super resolution imaging shows ubiquitination across the entire mitochondria. - The outer mitochondrial membrane is severed, allowing access to the inner membrane. - Cytochrome c is released from mitochondria due to the outer membrane's disruption. 47:13 🧪 Mass Spectrometry Analysis - Mass spectrometry confirms ubiquitination of inner mitochondrial membrane proteins. - Actinin-treated cells show ubiquitination of proteins inside the mitochondria. - Evidence supports the role of actinin-induced protein toxicity in mitochondrial changes. 48:52 🔬 Proteins on inner mitochondrial membrane are ubiquitinated. - Inner mitochondrial membrane proteins undergo ubiquitination. 49:21 🧬 Examining mitochondrial ubiquitination in a single mitochondrion. - Study focuses on mitochondrial ubiquitination in individual mitochondria. - Utilizing advanced microscopy technology for detailed analysis. 50:16 🧪 Examining the role of LC3 in autophagy. - LC3 is a marker of autophagy. - LC3 connects ubiquitinated proteins on mitochondria to autophagy machinery. 51:27 📊 LC3 presence indicates autophagy is occurring. - LC3 is found in proximity to mitochondria, implying autophagy. - Experiment using autophagy inhibitor still shows LC3-Mitochondria association. 52:23 🧪 Relationship between cytochrome c and autophagy markers. - Loss of cytochrome c is associated with outer mitochondrial membrane severing. - Autophagy markers are linked to the cytochrome c change. 54:43 🔬 Reintroduction of parkin in cells. - Introducing parkin via genetic engineering to cells lacking it. - Quantifying cytochrome c levels with and without parkin. 56:46 🧬 Parkin presence reduces high cytochrome c mitochondria levels. - Parkin reduces high cytochrome c mitochondria levels. - Autophagy inhibition eliminates parkin's effect. 59:21 🧪 Parkin affects classical ubiquitin phosphorylation pathway. - Parkin presence affects phosphorylation of ubiquitin. - Outer mitochondrial membrane integrity is preserved with parkin. 01:01:30 📝 Non-traditional autophagy pathway involving cytochrome c. - A non-traditional autophagy pathway involves cytochrome c accumulation. - Possible involvement of mitochondrial fission in initiating autophagy. 01:05:15 🧬 Recognition of inner mitochondrial membrane in autophagy. - Sudden exposure of inner mitochondrial membrane may trigger autophagy. - Speculation about mitochondria being recognized as a foreign object in autophagy. Made with HARPA AI

[@anahitawilson9682]

Very interesting. So do you think that a secondary mechanism of supplement CoQ10 is to support ubiquination as a first step towards autophagy? CoQ10 isn't normally associated with autophagy. Apologies if this is a completely irrelevant!

[@Physionic]

I honestly don't know. I think one of the major issues I have with supplementation is "will the supplement reach the cells intact?" - usually, it doesn't. Even if it does, will it be used? So, I haven't run across any studies on the matter, although I do have a video on CoQ10 for migraines, although I don't remember the implications on autophagy. Something to look into in the future, Anahita.

[@anahitawilson9682]

@@Physionic I think I would have to check if there are any in-vivo studies out there that employed 14C-CoQ10, to check on ADME. I'm intrigued by this supplement as it seems to alleviate side effects of tiredness resulting from Statin intake. So I wondered whether the mechanism might perhaps include mitophagy. Anyway thank you for responding.

[@anahitawilson9682]

@@Physionic www.ncbi.nlm.nih.gov/pmc/articles/PMC7278738/pdf/antioxidants-09-00386.pdf Science often poses more questions....good luck with your research!

[@tomaszrybarczyk630]

Wonderful journey into the modern research process. I' completely blown away! Thanks a lot and congratulations to the whole Lab.

[@danielcharlesfilms2897]

You're a great teacher! Even with little molecular biology knowledge I could follow.

[@Physionic]

Thanks, Daniel - that’s really kind of you, it makes me happy to heart teaching skills are up to par. Thank you.

[@DavidPaulNewtonScott]

Yea but if you are on this channel you are a great student. Astrophysics is easy by comparison.

[@Naomi_kyo]

Congratulations on your published paper! Love the graphs, so many key words I need to learn now :)

[@Physionic]

Thanks, Cindy! I appreciate you diving into some of these videos, seems you're quite interested in biology.

[@Naomi_kyo]

Yes! Thank u for sparking my interest. I didn’t even know the difference between an enzyme and a kinase. I need to re-enter elementary lol

[@margeretheath597]

Very exciting!

[@SimoneDrKoch]

Amazing! I enjoyed every second. Thank you for taking us to your work ❤️!

[@Physionic]

Thank you. Kind of you, Dr. Koch.

[@luckssj]

Thanks for sharing - this is fantastic Insite looking for more information - Have you looked at NMN and does this repair the Mitochondria?

[@rredding]

Okay, I understand all about Parkin, but how about his son? Ok, I HAD to say this, but thank you for this exciting insight in modern "protein-biology"! I am just at the level of thinking about practical way to improve health of my own mitochondria...

[@ArkadiProkopov]

Excellent, congratulations!

[@anahitawilson9682]

...and what are the autophagy mechanisms for OH-citrate, spermidine and resveratrol? Thinking of Dr Kroemer's work. I'm not a molecular biologist (background in chemistry) but learning about mechanisms in Nutrition. It's a all super interesting!

[@rredding]

Anita, only watching this 1 year after you did.... Exact the same question, I am about to check the later videos..

[@organicallypure1737]

Thank you for your work, I just about understood on a very basic level. My question given this info; given this learning, what could a person do to increase their LC3, P62 markers to promote autophagy in cancer cells that protect themselves from these proteins?

[@c4vette4fun]

I noticed you have a red panel in the background of some of your presentations. What happens to the mitochondria when exposed to the light?

[@tyrussteinman7491]

I know its been two years, but: After watching your video on mitochondria fission/elongation from fasting, it would seem you found hard evidence that fasting does reverse/prevent/treat conditions that arise from the build up of useless proteins. If im wrong please correct me. You seem to be saying here that elongated mitochondria (or mitochondria prevented from splitting) do not build up that protein in the membrane space. If fasting helps elongate mitochondria, does that point toward fasting preventing the build up of useless proteins in the mitochondria? If that build up does not trigger autophagy through the non traditional pathway?

[@rredding]

Great question. I hope it's followed up..

[@guysiberry3011]

I know nothing but was memerised throughout! Thank you.

[@Physionic]

Thank you, Guy - kind of you.

[@martijncrowe3901]

Very interesting. Txs took me various days to follow.

[@Physionic]

Ha, that's dedication - thank you for putting in such effort, Martjin.

[@damien2198]

"many many mitochondrias" funny I always pictured only one Mitochodria per cell, I should know better LOL

[@melt7891]

Thanks 😊

[@Physionic]

My pleasure, Mel.

[@robertsmyk4102]

I saw a video of cristae in alignment as mitochondria are touching each other and it would seem that they are in communication. Does this imply intelligence?

[@bobcocampo]

What test will show that you are in a state of autophagy?

[@christophercasanova3664]

If I became a doctor, aside from clinical work I will also do some basic medical research. For now I have my undergraduate degree in computer science, and few courses in life sciences and chemistry and physics, human anatomy and physiology but someday hopefully I could get into a medical school to learn more... And eventually pursue my interest in molecular medicine.

[@Physionic]

Sounds great, Christopher - good luck.

[@christophercasanova3664]

@@Physionic thank you for sharing your great research Sir!

[@DavidPaulNewtonScott]

This all implies that we can damage mitochondria and that they can be fixed. However, there has to be a blueprint, so where is that. Also how can we be kind to mitochondria eg dont eat cyanide (almonds) give the fats they like. One of your videos seems to imply they dont like oleic acid (olive oil) but like palm oil. Saturated, unsaturated, polyunsaturated, whats the score?

[@healthdecodedwithaltaf3647]

Excellent thanks ✨

[@christmassticker1044]

?? .?? ? 😑😑😉

[@christmassticker1044]

? 😙 😚.

[@christmassticker1044]

This wa.!

[@DavidPaulNewtonScott]

You da man and that being the case, I think you need to do a big job on castor oil.

[@Myrslokstok]

Ok the "M" inner structure are 3D "folds" and not "pillars".

[@joshuabowman7210]

what are the subset cells that don't have Mitochondria ? I thought only red blood cells gave up there mitochondria during maturation. I been studying the Mitochondria link to health and Cancer and Hormones and Vitamin D and the Microbial world we are and ect.

[@cristilaye5912]

Do you think FASTING can repair vaccine damage if a person only took one shot?

[@guysiberry3011]

mesmerised

[@sheradenart7907]

LOL. I must interject that emotions ARE chemical signals.

[@anroselarue]

Yeah. You look excited.

[@khamen723]

First question: What is mitochondria? Answer: We don’t know and we don’t know why they’re there, or who put them there. 😢😑

[@DetarLeflore]

thanks from china.

[@Physionic]

You're welcome, from the USA!

[@netto682]

👏👏👏🇧🇷

[@netto682]

Onde agem as MICOTOXINAS nas membranas

[@netto682]

?

[@TDRH]

Quite interesting that once the inner mitochondria membranes are exposed to the cell and the immune system cannot recognise them any more, just like the inner membranes are hide and sneak under the cloak of outter membranes to function as a power plant to the cell 😂

[@steves8014]

Huh?

[@khlim428]

So complicated