Cellular ATP demand creates metabolically distinct subpopulations of mitochondria, 2024, Ryu et al.

Cellular ATP demand creates metabolically distinct subpopulations of mitochondria
Ryu, Keun Woo; Fung, Tak Shun; Baker, Daphne C.; Saoi, Michelle; Park, Jinsung; Febres-Aldana, Christopher A.; Aly, Rania G.; Cui, Ruobing; Sharma, Anurag; Fu, Yi; Jones, Olivia L.; Cai, Xin; Pasolli, H. Amalia; Cross, Justin R.; Rudin, Charles M.; Thompson, Craig B.

Mitochondria serve a crucial role in cell growth and proliferation by supporting both ATP synthesis and the production of macromolecular precursors. Whereas oxidative phosphorylation (OXPHOS) depends mainly on the oxidation of intermediates from the tricarboxylic acid cycle, the mitochondrial production of proline and ornithine relies on reductive synthesis. How these competing metabolic pathways take place in the same organelle is not clear.

Here we show that when cellular dependence on OXPHOS increases, pyrroline-5-carboxylate synthase (P5CS)—the rate-limiting enzyme in the reductive synthesis of proline and ornithine—becomes sequestered in a subset of mitochondria that lack cristae and ATP synthase. This sequestration is driven by both the intrinsic ability of P5CS to form filaments and the mitochondrial fusion and fission cycle. Disruption of mitochondrial dynamics, by impeding mitofusin-mediated fusion or dynamin-like-protein-1-mediated fission, impairs the separation of P5CS-containing mitochondria from mitochondria that are enriched in cristae and ATP synthase. Failure to segregate these metabolic pathways through mitochondrial fusion and fission results in cells either sacrificing the capacity for OXPHOS while sustaining the reductive synthesis of proline, or foregoing proline synthesis while preserving adaptive OXPHOS.

These findings provide evidence of the key role of mitochondrial fission and fusion in maintaining both oxidative and reductive biosyntheses in response to changing nutrient availability and bioenergetic demand.

Link | PDF (Nature)

 

My mitochondria and the rest of me are at odds over what my bioenergeric demand is.

 

I suppose it's like any other bacteria in a changing environment. Change a factor, such as oxygen or fuel, and the bacteria change themselves or their offspring. The interior of a cell is a rapidly changing environment, so the bacteria (mitochondria) evolved to respond rapidly.

I wonder whether technology is up to the task of monitoring mitochondrial sub-types in-situ, to see whether there are abnormalities in PWME.