Daniel Kane
@mitokanedria
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“...Time is the fire in which we burn.” -Delmore Schwartz 🪡 🧵 thread about #lactate oxidation and metabolic heat 🔥. /1 https://t.co/1GtHz17z5e
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Wonderful to have played a small role in this effort. This century of biochemistry will place the staggering numeracy in the systems we study at the forefront of our science. Looking forward to more thinking like this👏 #Biochemistry #Redox #Bioenergetics
Pleasure to collaborate with @PanosChatz1 and @CAS_ReproLab on this work dealing with the i-space a proteoform centric theory of redox regulation
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Here's the link to the paper. Download in the next 50 days for free! @ECU_Biology @ECUResearch @EastCarolinaDOI
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New publication from my lab about the metabolic (mitochondrial) effects of Yerba Mate (YM). We found disparate effects of YM in fat tissue and muscle tissue. In fat, YM increased metabolic rate (via greater mitochondrial uncoupling). However, in muscle, YM had no such
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🔥thread alert: origins of the Crabtree effect
Time for summer fun 🌞⛱️: let's talk about the Crabtree effect 🦀🦀, an ultimate #metabolismclassic, describing the ability of glucose to represses mitochondrial respiration https://t.co/JSqyd1et3p 1/n
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The pyruvate dehydrogenase complex: Life’s essential, vulnerable and druggable energy homeostat. By P.W. Stacpoole and C.E. McCall. 2023. 🔥 https://t.co/a4Jm1NapSK
pubmed.ncbi.nlm.nih.gov
Found in all organisms, pyruvate dehydrogenase complexes (PDC) are the keystones of prokaryotic and eukaryotic energy metabolism. In eukaryotic organisms these multi-component megacomplexes provide a...
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“In conclusion, lactate is less effective than glucose and potentially detrimental during neural network rhythms featuring high energetic costs, likely through the lack of some obligatory ATP synthesis by aerobic glycolysis at excitatory and inhibitory synapses.���
Lactate as a supplemental fuel for synaptic transmission and neuronal network oscillations: Potentials and limitations - PubMed
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Ruh-roh! Concentration dependent?
Dramatic change in the shape of mitochondria after addition of digitonin
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Excited to announce our group's latest preprint led by @IlyaNBoykov + @Mcmontgomery11
https://t.co/6ugOG5Vm1Q In it we compared OXPHOS expression/function, across various murine tumor types, matched normal tissues and other organs -- all normalized to mito content. 🧵below
biorxiv.org
Targeting mitochondrial oxidative phosphorylation (OXPHOS) to combat cancer is increasingly being investigated using a variety of small molecule inhibitors. Clinical success for these inhibitors has...
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A mechanistic link between the hyperglycemia of T2D and Alzheimer’s Disease involving KATP channels 👇
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Otto Warburg (of the “Warburg effect”) features prominently in Bound by Muscle as a mentor to Meyerhof.
More about this in recently published book, Bound by Muscle: Biological Science, Humanism, and the Lives of A. V. Hill and Otto Meyerhof
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The periodic table of elements came to Mendeleev in a dream?!
themarginalian.org
“Awakening, I immediately wrote it down on a piece of paper.”
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“An important, unresolved issue in these studies is that the carbohydrate taken up in excess of oxygen during exhaustive exercise does not accumulate in brain (2)...” – G. Dienal, 2019 (1) 1. https://t.co/6TTuFCzI38 2. https://t.co/wkjUFSz5zr
The ⬇️ in 🧠 O2/[glucose+0.5lactate] with exerc has been interpreted to reflect declining complete oxidation but not accumulation of glucose and lactate taken up by the 🧠. /20 https://t.co/jHniLuhQ5p
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More on this from Brooks: https://t.co/u7aX1CL3NW And a podcast:
foundmyfitness.com
Dr. George Brooks discusses the metabolic pathway known as the “lactate shuttle" and its role in the recovery from traumatic brain injury.
This view was revised for mammalian metabolism vis-a-vis @GeorgeABrooks3’s Lactate Shuttle model. First conceived by Brooks (1985), a central tenet of the model was that lactate travels within and between cells as an oxidizable fuel /7 https://t.co/GfdUEWvOcZ
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“Lactate is the universally available form of carbohydrate” - J. Rabinowitz, 2022 👆More about this in podcast form: https://t.co/yToeyyKTLj The important role of #lactate as an alternate fuel begins around 36:30.
peterattiamd.com
"My big hope is that we're going to be able to have some combination of directed, metabolic immune supplements and diet that really work with therapy to treat cancer.” —Josh Rabinowitz
While research has increasingly confirmed Brooks’ model and the centrality of lactate metabolism (e.g., https://t.co/np2k8Ige9Q
@realTonyHui), work on the physical bioenergetics of lactate metabolism has been relatively sparse since the time of Hill & Meyerhof. /8
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More about this in recently published book, Bound by Muscle: Biological Science, Humanism, and the Lives of A. V. Hill and Otto Meyerhof
In 1923, BFFs A.V. Hill and Otto Meyerhof split the Nobel Prize in Physiology or Medicine for their discoveries relating to the production of heat in muscle (Hill), and the relationship between oxygen consumption and lactate metabolism in muscle (Meyerhof). /5
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Shout out to collab’s Alex Foo, Erin Noftall, Karen Brebner, and @gmsprezman And to the helpful reviewers, one of whom (revealed later to be THE Lee Hansen) provided exceptional feedback and guidance. ✌️/fin
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TL;DR we found the rate of heat production in lactate-fed mitochondria to be intriguingly low in mammalian brain, and suggest a model in which lactate serves a thermoregulatory function in the 🧠. /30 https://t.co/1GtHz17z5e
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Whole-body and localized-regional hyperthermia has been used as a cancer treatment alone or in combo with others. /29 https://t.co/oGxxwc5dqT
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