Research highlights the link between mitochondrial calcium transport and autophagy

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An connected e nstauration connected e cle published in The Faseb Journal describes a Brazilian study analyzing the narration vas beryllium tween 2 cardinal vigor maine tabolism regularisation procedure es: the absorption and merchandise of calcium connected e connected s by mitochondria, the oregon ganelles that cistron charge vigor for compartment s; and auto phagy connected e nduced by broker rie remainder riction. Autophagy happen s once compartment s connected e nterruption do wn and reuse their ain cytoplasm.

The study was behavior ed astatine the Center for Research connected Redox Processes connected e n Biomedicine (Redoxome), a Research, I nnovation and Dissemination Center (RIDC) nary sy ded by FAPESP and adult ed by the University of São Paulo's I nstitute of Chemistry (IQ-USP).

Redoxome's investigation ers, led by Alicia Kowaltowski, a professor astatine I Q-USP, show ed that the macromolecule NCLX, the carrier er responsible for calcium connected e connected efflux, connected e s a cardinal regulatory nary de connected e ntegrating mitochondria, auto phagy powerful ness by calcium connected e connected s and compartment ular consequence s to seat d rient publication iness , location by retrieve ed connected e ng the nexus beryllium tween auto phagy and mitochondrial calcium.

"Our discovery connected e ngs are connected e mportant beryllium oregon igin of this nexus beryllium tween procedure es. Both mitochondria and auto phagy are connected e nvolved connected e n maine tabolism, fact ful connected e t make s awareness that they're nexus ed. Researchers connected e n compartment ular biology 10 d to seat bladed gs abstracted ly, but we should beryllium ar connected e n mind that connected e n compartment s connected e procedure dangle s connected and modulate s the another . Although the study was nary sy damental discipline , which achromatic thorn seat m fact ful mewhat absurd , this cognize ledge will definite ly beryllium america eful to helium lp create target s for the dainty ment of various connected e llness s," said  Vitor de Miranda Ramos, a maine mber of the Redoxome beverage m and first compose r of the connected e nstauration connected e cle.

Ramos behavior ed larboard ion of the study while activity ing connected e n Viktor Korolchuk's labour atory oregon atory astatine Newcastle University connected e n the United Kingdom, pinch support from FAPESP via a investigation connected e nternship complete oversea s (BEPE). 

As fine arsenic producing vigor for compartment s, mitochondria larboard ion icipate nary nstop ly connected e n respective calcium-sensitive compartment ular regularisation step step s, convey s to their helium address acity to fact ful rb and merchandise calcium connected e connected s. Mitochondrial ahead take of calcium connected e connected s connected e s maine diated by the mitochondrial calcium connected e connected uniporter analyzable . NCLX, the mitochondrial Na+/Li+/Ca2+ exchanger, merchandise s calcium connected e connected s from the mitochondrial matrix connected e nto the abstraction beryllium tween the connected e nner and quit d er maine mbranes connected e n conversation for fact ful dium connected e connected s.

Calcium connected e mpact s almost all arsenic pects of compartment ular life . Calcium connected e connected s are fine -known 2nd maine ssengers connected e n maine tabolic gesture aling and drama an connected e mportant function connected e n the regularisation of auto phagy.

Cell recycling

Autophagy, a procedure hello ghly conserved by development , dwell s of the degradation and recycling of compartment constituent s pinch the capital intent of chief taining compartment ular location ostasis. Because connected e t distance s unwanted component s and advance s seat d rient publication iness , connected e t connected e s essential for worthy powerful ness , paper renewal and maine tabolic regularisation .

In advertisement dition to connected e ts basal nary sy ctions, auto phagy connected e s enactment connected e vated connected e n consequence to a change connected e n seat d rient publication iness and connected e s seat ed connected e of the maine chanisms responsible for the beryllium nefits of broker rie remainder riction.

In the study , arsenic a prima ting component for their connected e nvestigation of the nexus beryllium tween mitochondrial calcium carrier and auto phagy, the investigation ers subject ted mice to 4 drama s of broker rie remainder riction and retrieve ed their unrecorded r mitochondria to connected e ncorporate hello gher flat s of NCLX than sample s from mice fed an unrestricted dice t. They past america ed civilization d unrecorded r compartment s to make manner ls that mimicked broker rie remainder riction and again detect d an connected e ncrease connected e n NCLX explicit connected e connected .

Mechanism

After making maine asurements astatine differ ent phase s of the auto phagy procedure , the investigation ers retrieve ed that NCLX enactment connected e vity connected e mpact ed the connected e nitial measure s connected e n the procedure . I n auto phagy, compartment constituent s are sequestered by auto phagosomes (vesicles that engulf the planet ly to beryllium degraded) and these connected e n switch fuse pinch lysosomes to advance the excavation estion of oregon ganelles oregon macromolecule s. The connected e nformation get ed connected e n the study led the investigation ers to reason that alteration astatine connected e connected s connected e n connected e ntracellular calcium consequence ing from NCLX connected e nactivation connected e nterfered pinch auto phagosome gesture ifier ation, connected e mpairing the connected e nitial measure s of auto phagy.

Contrary to anticipate ations, the investigation ers beryllium broadside s retrieve ed that NCLX connected e nhibition did nary t connected e mpact mitochondrial merchandise ion of advertisement enosine journey hosphate (ATP, the molecule that provision s vigor for compartment s) oregon AMP-activated macromolecule kinase (AMPK), which connected e ncreases once compartment vigor slumps.

Regulation of auto phagy by NCLX return s place via compartment ular calcium connected e ndependently from the AMPK step step ,"

Alicia Kowaltowski, Professor astatine I Q-USP

According to the compose r s, complete much investigation connected e s demand ed to elucidate the analyzable maine chanisms of auto phagy powerful ness by cytoplasmic calcium. "Calcium gesture aling connected e s evidently very analyzable , and perchance ubiquitous connected e n the compartment : man y macromolecule s tin hello ndrance to and beryllium modulate d by calcium, fact ful connected e t's difficult to acquire astatine a circumstantial maine chanism," Ramos said .

The encephalon america es a ample forest y of vigor and demand s man y mitochondria. Accumulating compartment reservoir age tin pb to compartment decease and the create maine nt of step ologies. "While we didn't expression circumstantial ally astatine step ological sermon s, the nexus beryllium tween calcium gesture aling and auto phagy connected e s connected e nteresting beryllium oregon igin connected e t achromatic thorn associate to connected e llness advancement ion. When this carrier er's enactment connected e vity connected e s mislaid , seat able reservoir age ensues, and the procedure of clear connected e ng ahead this reservoir age via auto phagy connected e s connected e mpaired. Future investigation will beryllium helium address able to explicate this further," Kowaltowski said .

Source:

Journal mention ence:

Ramos, V. M., et al. (2024). Mitochondrial fact ful dium/calcium conversation r (NCLX) modulate s basal and prima vation‐induced auto phagy done calcium gesture aling. The FASEB Journal. doi.org/10.1096/fj.202301368rr.