Thread by @DrJackKruse

Mitochondria are constantly undergoing changes in morphology & distribution within the cytoplasm, as fused (network forming) or fissioned (punctate) mitochondria. When there’s a problem w/ fission, circadian control is lost. The consequences can include neurodegenerative diseases

https://twitter.com/DrJackKruse/status/1513672249928294402

3/For years we have known that one particular protein, called Drp1, is a master regulator of mitochondrial fission. Drp1 is phosphorylated in a circadian-dependent manner, thus varying its activity according to light/dark cycles

4/Your colony of mitochondria is an integrative information/energy hub coordinating circadian rhythms, metabolism, hormone release, melatonin production, & control of the human microbiome species, as well as immune function.

5/ Circadian rhythmicity is also regulated by a set of peripheral “clock proteins,” which form a hierarchy of oscillators that function at the cellular, tissue, and systems levels and are composed of at least three feedback loops.

6/ Most PhDs know about them but have no idea how they operate.

7/One loop depends on the heterodimerization of the transcription factors brain/muscle aryl hydrocarbon receptor nuclear translocator-like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK)

8/ When CLOCK binds to E-box elements, it induces the expression of their own repressors, named Period (PER) and Cryptochrome (CRY) proteins

9/Since these proteins (PER-1, -2, and -3, and CRY-1 and -2) are gradually degraded, the expression on BMAL1 and CLOCK ceases, starting a new circadian cycle. This renews the circadian mechanism.

10/A second loop is formed by the nuclear retinoic acid receptor-related orphan receptor (ROR) (α, β, γ) and REV-ERB (α, β), which, upon activation by the BMAL1/CLOCK heterodimer and translocation into the nucleus. This confuses many PhDs.

11/Rev-erbs bind to receptor-related orphan receptor response elements (ROREs) in the promoter of BMAL1, regulating the expression of BMAL1

12/A third loop is formed by the transcriptional activator albumin D-box binding protein (DBP) and the repressor nuclear factor interleukin 3 (NFIL3), which synergistically regulate the expression of D-box genes, including the Per genes.

13/The interplay between these three regulatory loops is at the core of circadian rhythmicity and clock-related gene expression. Mitochondrial dynamics of fission and fusion control the circadian mechanism and most hormone release

14/Mitochondria regulate circadian rhythmicity through NAD+ production, SIRT1 & SIRT3 activation & mitochondrial dynamics. SIRT1 and SIRT3 activity is HDACs is dependent on NAD+. SIRT1 and SIRT3 counteract CLOCK; NAD+ synthesis is highly dependent on proper circadian rhythmicity

15/ NAD+ synthesis at cytochrome 1 is highly dependent on circadian rhythmicity, and this is related to mitochondrial dynamics of fission and fusion being operational. Heteroplasmy rate destroys this balance.

16/ Fused mitochondria are regarded as metabolically more active than fragmented mitochondria, as cells with a fused mitochondrial network seem to have a higher respiratory rate than cells with fragmented mitochondria

17/Data has been suggested that there is a correlation between circadian rhythmicity and mitochondrial function. Cells with disrupted mitochondria (heteroplasmy rate), such as Rho 0 cells, lack a well-defined circadian rhythmicity

18/ Why? This happens in part due to the lack of the characteristic robust oscillatory respiratory activity observed in cells with healthy mitochondria (Scrima et al., 2016).

19/Lactate is a natural ligand for the GPR81 cell membrane receptor that recognizes other monocarboxylates; lactate enhances cell differentiation, suppresses T-cell proliferation, reduces cytotoxic capacity of cytotoxic T lymphocytes, stimulates gene expression,roles in the tumor

20/ Glycolysis and Krebs cycle-derived metabolites, as well as microbiota-derived metabolites, exert biological functions beyond energetic and biosynthetic metabolism. This is part of information transfer buried in energy metabolism = Wheeler and Shannon theorems on entropy

21/ The way information is buried in metabolism is based on the charge density variation of these intermediates and the electronic configuration of their atoms

22/ Sunlight alters charge density. This is SOMETHING no biological PhDs have any concept of. It is not in their paradigm. Rev-erbs are the key to that mystery.

23/ All metabolic intermediates are hydrated. Water is sensitive to electric and magnetic fields. It charge separates under the force of light photons. When light hits water an exclusion zone forms which has a larger net negative charge than one would expect = charge density

24/In animals electrical information generated in mitochondria is more crucial than genes. It turns out charge density variation is the key to understanding what life is really up to when it is connected to the decentralized systems of Nature.

25/How? As the Sun rotates, its magnetic field twists into an Archimedean spiral, as it extends through the solar system. This phenomenon is often called the Parker spiral of the interplanetary magnetic field.

26/The spiral nature of the heliospheric magnetic field was noted earlier by Hannes Alfvén, based on the structure of comet tails. All living things on Earth are affected by this magnetic sheet in the solar wind via their mitochondria.

27/ Remember blood (rev-erb) and water are both Newtonian magnetohydrodynamic fluids that respond to this sheet. The influence of this spiral-shaped magnetic field on the interplanetary medium (solar wind) creates the largest charged structure in the Solar System

28/ The charged structure is called the heliospheric current sheet. Parker's spiral magnetic field was divided in two by a current sheet seen in the picture.

29/ No one I know in biology seems to understand how the solar wind changes the structural basis by which REV-ERBβ. The electronics in sunlight can differentiate between a porphyrin agonist and antagonist in RBCs due to Rev erb. It is tied to charge density alterations.

30/ subtle changes in the porphyrin metal center due to ring conformation influence the agonist vs antagonist action of porphyrins due to sunlight alters gas binding to the iron metal center heme that drives circadian alterations in REV-ERB activity

31/ The light of our star uses the lightest atoms on the periodic table and the clock mechanism in cells reflects this redox choice by light. You must now want to know how Nature chose this path. It is all about the decentralization of energy and information flow.

32/ Nature tapped the unique chemistry of the lightest elements. The chemistry of the second-period element of each group (n = 2: Li, Be, B, C, N, O, and F) differs in many important respects from that of the heavier members, or congeners, of the group.

33/ The elements of the third period (n = 3: Na, Mg, Al, Si, P, S, and Cl) are generally more representative of the group to which they belong.

34/ The anomalous chemistry of second-period elements results from three important characteristics: small radii, energetically unavailable d orbitals, and a tendency to form pi (π) bonds with other atoms. All critical to creating - entropy life requires

35/ Due to their small radii, second-period elements have electron affinities that are less negative than would be predicted from general periodic trends. When an electron is added to a small atom, increased electron–electron repulsions tend to destabilize the anions in cells

36/ Moreover, the small sizes of these elements prevent them from forming compounds in which they have more than four nearest neighbors. This makes them smaller = thermodynamically more efficient = low power needed for action

37/Because of the smaller atomic size, simple binary ionic compounds of second-period elements also have more covalent character than the corresponding compounds formed from their heavier congeners.

38/ The very small cations derived from 2nd-period elements have a high charge-to-radius ratio and can therefore polarize the filled valence shell of an anion.

39/ As such, the bonding in such compounds has a significant covalent component, giving the properties of the compounds that can differ significantly from those expected for simple ionic compounds. Covalent bonds are easier for sunlight to break and rearrange.

40/As an example, LiCl, which is partially covalent in character, is much more soluble than NaCl in solvents with a relatively low dielectric constant, such as ethanol (ε = 25.3 versus 80.1 for H2O). IMPLICATIONS???

41/ Because d orbitals are never occupied for principal quantum numbers less than 3, the valence electrons of second-period elements occupy 2s & 2p orbitals only. Energy of the 3d orbitals exceeds the energy of 2s & 2p orbitals, using them in bonding is energetically prohibitive

42/ This electronic configuration issue is why biologists never have understood the clock mechanism well. Their knowledge of chemistry and physics blows.

43/ Consequently, electron configurations with more than four electron pairs around a central, second-period element are simply not observed on Earth. IMPLICATIONS OF THIS???

44/This is why Nature’s semiconductors are all carbon based and hydrated. Charge density and a strong dielectric ability is critical to the living state. This is the physical basis of how a negative entropy state is built.

45/ This is the physical basis of how a negative entropy state is built - Schodinger's 1944 book, What is Life.

Does charge density affect entropy?
Yes it does.

46/ Entropy is linked by the work of Wheeler and Shannon. Entropy = energy and information. Biology is unaware that energy and information are equivalent.

47/ Most importantly, while charge density of cations or anions correlates with the translational entropy loss, anions with similar charge density as that of cations has a much stronger and long-range effect on water.

48/How do ions affect cell water?
Small ions (kosmotropes) have high charge densities so they cause strong electrostatic ordering of nearby waters, breaking H-bonds. In contrast, large ions (chaotropes) have low charge densities, and surrounding water molecules are H- bonded.

49/Water hit by the sun form an exclusion zone that causes water to take on the crystalline form of H3O2. This adds massive electronegativity to water networks.

50/ In 1666 Isaac Newton discovered that sunlight could be split into different wavelengths of light that behave uniquely. Very few people seem to know how those frequencies in light alter water network chemistry.

51/ Since then light has been studied extensively. Very few in professional science have asked how light changes water. That water than changes the electronic density of proteins in cells

Do ions disrupt hydrogen bonds? The interface of water and DNA is a sea of H-bonds

52/ The ions having the highest charge densities (F−, for example) are the most disruptive of water–water hydrogen bonding. Fluoride is a dielectric blocker in water. It lowers the ability to transfer or transmute energy and information.

53/One of the most dramatic differences between the lightest main group elements and their heavier congeners is the tendency of the second-period elements to form species that contain multiple bonds. pi electrons bonds are big in the living state

54/ A C=C bond, for example, is approximately 80% stronger than a C–C bond. In contrast, an Si=Si bond, with less p-orbital overlap between the valence orbitals of the bonded atoms because of the larger atomic size, is only about 40% stronger than an Si–Si bond.

55/ This is why life's semiconductors are all carbon based and your tech gear uses silicon. It is also why technology will never replace the living state. The electronics are more favorable for carbon over silicon

56/The crystal structure of CoPP-bound REV-ERBβ causes conformational changes induced by sunlight on CoPP compared with heme: it adopts a planar conformation as opposed to the puckered conformation observed in the heme-bound REV-ERBβ crystal structure. Life is electronic via sun

57/ When your PhD experts and functional medicine guys get to this level, then come talk to me. Decentralized medicine and mitochondriacs are way ahead of their paradigm of health.

58/ In each of our cells, there is a fractal network of carbon nanotubes that constricts water to a certain dimension to make quantum magic happen using the photoelectric effect and allow free use of protons to flow in the molecular network of water. We call this protonicity.

59/ This is the + charge current in cells. The current is much higher when the particle being moved has mass. Electrons have 1/1836th the mass of a proton. Light is what energizes electrons. Red light is what moves protons (1535nm)

60/ In our electric universe, galaxies are created within helical currents that form a great circuit through intergalactic space. The Bennett pinch effect squeezes plasma inside these cosmic “transmission lines” compressing clouds of ionized plasmas within electromagnetic fields

61/ The solar plasma compresses protons & their positive charges, igniting stars like our sun by forming toroidal currents around galactic equators. Those suns then send their light to planets. The light of the star is a cathode ray. Planets are anodes in this electric circuit

62/ On Earth, a physio-chemical redox evolution created hydrated semiconductors that turn the sun's light back into an electric plasma called the DC electric current.

63/ The DC electric cuurent in mitochondria helps regenerate all animals and plants on the surface of this planet. Just a remarkable circle of life-based upon natural electric power and the mysteries based on sun light

64/When an applied magnetic field is added to the new environment the atoms in our mitochondria are immediately affected. How? The orbital motion of electrons is altered to produce a magnetic moment in the opposite direction to the applied magnetic field from the new environment

65/When you consider that the electromagnetic force gets infinitely stronger as scale shrinks things really begin to make sense when you consider the power generation in mitochondria. The inner mitochondrial membrane is 6 microns.

66/ The electric state of a cell is determined by many complex factors, but it is clear redox power is the critical factor. What are some of the other factors that augment redox power? The opening & closing of ion channel proteins which control movements of ions across membranes

67/Changes in the cells’ electrical potential via the activity of ion channels are shown to be able to suppress or trigger cancer. The chemical changes are always preceded by electrical changes in cells. These changes are wholly tied to the redox state in that cell system

68/This is how ALAN and abnormal electric and magnetic fields from technology lead to disease. Another factor is electrical synapses that transfer electricity from one cell to another via their membrane system.

69/ Light frequencies have different electromagnetic footprints that lead to different change densities. Those changes are accounted for by Rev-erb proteins and that is what alters proteins/genes in cells.

70/ That system is adjacent to the cell water. Therefore, membrane integrity and water fidelity in cells should be factors of critical importance to redox potential and to health.

71/Charge conservation isn't like energy conservation ideas in the laws of thermodynamics. This offends people who do not understand the nuance of this science. Energy cannot be created or destroyed. Neither can charge but this is where you need to pay deep attention to details

72/ This is why charges matter more than energy flow for cells and their mitochondria. Charge confirmation does not mean that individual positive and negative charges cannot be created or destroyed. Why?

73/Electric charge is ONLY carried by the two charged subatomic particles such as electrons and protons. Charged particles that carry electrical information and energy can be created and destroyed in elementary particle reactions.

74/We see this every day CERN operates. It turns out varying redox potential allows for the alteration of electrons and protons inside mitochondria and many other organelles in cells. That electrical variation of charges creates tipping points in cells.

75/ What biologists, PhDs, MDs fail to realize is that mitochondria only use electrons and protons for the SAME reason. It is the basis of how life does the things it can. It changes charge density with light.