Mitochondrial signal transduction, 2022, Picard and Shirihai

[SNT Gatchaman]

Mitochondrial signal transduction
Picard M, Shirihai OS

The analogy of mitochondria as powerhouses has expired. Mitochondria are living, dynamic, maternally inherited, energy-transforming, biosynthetic, and signaling organelles that actively transduce biological information. We argue that mitochondria are the processor of the cell, and together with the nucleus and other organelles they constitute the mitochondrial information processing system (MIPS).

In a three-step process, mitochondria (1) sense and respond to both endogenous and environmental inputs through morphological and functional remodeling; (2) integrate information through dynamic, network-based physical interactions and diffusion mechanisms; and (3) produce output signals that tune the functions of other organelles and systemically regulate physiology.

This input-to-output transformation allows mitochondria to transduce metabolic, biochemical, neuroendocrine, and other local or systemic signals that enhance organismal adaptation. An explicit focus on mitochondrial signal transduction emphasizes the role of communication in mitochondrial biology. This framework also opens new avenues to understand how mitochondria mediate inter-organ processes underlying human health.

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[SNT Gatchaman]

Most recently, the omics era and a new quantitative handle on intermediate metabolism have cast mitochondria as biosynthetic and signaling organelles that produce signals influencing cell and organism behaviors via metabokine/mitokine signaling, mito-nuclear crosstalk, and remodeling of the epigenomic machinery across species. Through these theoretical transitions, mito-chondria have become the most studied organelle in the biomedical sciences.

 

[SNT Gatchaman]

Generally looks like a good overview of current biological concepts.

Outside of their intracellular roles as organelles, mitochondria also operate beyond the confines of the cell. They undergo physical transfer from cell to cell, influence neurotransmitter metabolism and inter-cellular communication at the neural synapse, synthesize all circulating steroid hormones that ensure sexual reproduction and species survival in mammals, and as discussed below, even contain receptors for systemic hormones. These discoveries are not only blurring cellular boundaries, but also revealing mitochondria in a light that emphasises communication—i.e., the bidirectional transfer of information from organelle to organism—as a natural aspect of their biology.

But also encompasses the mind-body interface!

energy metabolism in general and mitochondria in particular play permissive and instructive roles in stem cell differentiation and in the acquisition of immunometabolic phenotypes, influence whether animals are socially dominant or submissive, and influence how multiple organ systems in mice respond to evoked stress. In humans, mitochondrial energy production capacity also appears to dynamically respond to subjective psychosocial experiences, providing a foundation to begin understanding the mind-mitochondria connection.

 

[Wonko]

So what's their game? What are they really up to? What, in short, do mitochondria want out of life.

coz it certainly sounds like they are in charge, that 'we' are just the meat cities in which they live, so having some idea of what they 'want' might be a good thing.

 

[SNT Gatchaman]

One of the most powerful types of mammalian hormones are steroid molecules, broadly categorized into three major classes: (1) the sex-defining testosterone, estrogens, and progestins produced in the gonads; (2) the stress hormones that promote stress adaptation via metabolic and salt balance regulation including glucocorticoids and mineralocorticoids produced in the adrenal glands; and (3) neurosteroids produced in the nervous system.

Mitochondria produce steroid hormones from cholesterol, the initial substrate to all steroids.

Mitochondrial synthesis of systemically acting steroids occurs rapidly within minutes, and its synthesis arrest is equally rapid. The rapid, redox-sensitive, protein import-dependent regulation of this process illustrates how multiple intrinsic factors can influence mitochondrial steroidogenic outputs.

The evolutionary basis for positioning steroidogenesis in mitochondria remains uncertain but may have involved the uniquely reducing conditions of the mitochondrial matrix.

Developmentally, steroid hormones drive energetically expensive transcriptional and physiological programs that must incur substantial cellular energetic costs in target tissues. As a result, it is possible that to optimize fitness, these hormones should only be produced in proportion with the energetic capacity of target tissues. Assuming that the function of mitochondria is partially harmonized across both source steroidogenic and target catabolic energy-consuming tissues,
we postulate that the mitochondrial localization of steroidogenesis enzymes may reflect the product of system-level adaptation aiming to couple mitochondrial bioenergetic capacity and steroid hormone signaling across the organism.

 

[SNT Gatchaman]

So what's their game? What are they really up to? What, in short, do mitochondria want out of life.

Maybe we can only ask that question because of our mitochondria. Maybe they're the ones asking?

Did the role of mitochondria as an information processing system contribute to the evolutionary turning point of endosymbiosis? Argument accounting for the role of mitochondria as a harbinger of multicellular, complex life includes the protection from oxygen and a rise in energy supply, although these possibilities have been challenged. Communication and information exchange via optimized biological structures—epitomized at the scale of the organism by the nervous system—afforded an unprecedented acceleration and complexification of social behaviors among animals. This raises the possibility that the acquired ability of cells to sense their environment, efficiently transduce information, and communicate with each other via the [Mitochondrial Information Processing System] may have been a decisive factor in the evolution and diversification of multicellular life.