Regulation of Mitochondrial Complex I Biogenesis in Drosophila Flight Muscles

Garcia, Christian; Khajeh, Jahan; Coulanges, Emmanuel; Chen, Emily I-ju; Owusu-Ansah, Edward

doi:10.1016/j.celrep.2017.06.015

Cited by 62 publications

(106 citation statements)

References 39 publications

(48 reference statements)

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“…The lack of increase in complex I detected by BN‐PAGE may be also the result of a large portion of the complex participating in a supercomplex structure as shown previously in mouse TA muscle (Garcia et al . ). Similar to the results reported in the present study, cardiac muscle oxidative phosphorylation capacity also appears to undergo a major developmental transition (Piquereau et al .…”

Section: Discussionmentioning

confidence: 97%

Protein composition of the muscle mitochondrial reticulum during postnatal development

Kim

Yang

Katti

2019

The Journal of Physiology

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Key pointsr Muscle mitochondrial networks changed from a longitudinal, fibre parallel orientation to a perpendicular configuration during postnatal development.r Mitochondrial dynamics, mitophagy and calcium uptake proteins were abundant during early postnatal development.r Mitochondrial biogenesis and oxidative phosphorylation proteins were upregulated throughout muscle development.r Postnatal muscle mitochondrial network formation is accompanied by a change in protein expression profile from mitochondria designed for co-ordinated cellular assembly to mitochondria highly specialized for cellular energy metabolism.Abstract Striated muscle mitochondria form connected networks capable of rapid cellular energy distribution. However, the mitochondrial reticulum is not formed at birth and the mechanisms driving network development remain unclear. In the present study, we aimed to establish the network formation timecourse and protein expression profile during postnatal development of the murine muscle mitochondrial reticulum. Two-photon microscopy was used to observe mitochondrial network orientation in tibialis anterior (TA) muscles of live mice at postnatal days (P) 1, 7, 14, 21 and 42, respectively. All muscle fibres maintained a longitudinal, fibre parallel mitochondrial network orientation early in development (P1-7). Mixed networks were most common at P14 but, by P21, almost all fibres had developed the perpendicular mitochondrial orientation observed in mature, glycolytic fibres. Tandem mass tag proteomics were then applied to examine changes in 6869 protein abundances in developing TA muscles. Mitochondrial proteins increased by 32% from P1 to P42. In addition, both nuclear-and mitochondrial-DNA encoded oxidative phosphorylation (OxPhos) components were increased during development, whereas OxPhos assembly factors decreased. Although mitochondrial dynamics and mitophagy were induced at P1-7, mitochondrial biogenesis was enhanced after P14. Moreover, calcium signalling Y. Kim and others J Physiol 597.10 proteins and the mitochondrial calcium uniporter had the highest expression early in postnatal development. In conclusion, mitochondrial networks transform from a fibre parallel to perpendicular orientation during the second and third weeks after birth in murine glycolytic skeletal muscle. This structural transition is accompanied by a change in protein expression profile from mitochondria designed for co-ordinated cellular assembly to mitochondria highly specialized for cellular energy metabolism.

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Section: Discussionmentioning

confidence: 97%

Protein composition of the muscle mitochondrial reticulum during postnatal development

Kim

Yang

Katti

2019

The Journal of Physiology

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“…sembly of proteins and lipids. While it is known that proteins form well-defined complexes (1,2), supercomplexes (3)(4)(5), and mesoscopic structures (6,7), the assembly of lipids, their selforganization and their interactions, are not as clearly understood. Among the mitochondrial lipids, cardiolipin (CL) is particularly important because it binds tightly to proteins (8)(9)(10) and increases substantially their propensity to cluster and to form supercomplexes (11)(12)(13).…”

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confidence: 99%

Assembly of the complexes of oxidative phosphorylation triggers the remodeling of cardiolipin

Murari

Donelian

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Cardiolipin (CL) is a mitochondrial phospholipid with a very specific and functionally important fatty acid composition, generated by tafazzin. However, in vitro tafazzin catalyzes a promiscuous acyl exchange that acquires specificity only in response to perturbations of the physical state of lipids. To identify the process that imposes acyl specificity onto CL remodeling in vivo, we analyzed a series of deletions and knockdowns in Saccharomyces cerevisiae and Drosophila melanogaster, including carriers, membrane homeostasis proteins, fission-fusion proteins, cristae-shape controlling and MICOS proteins, and the complexes I–V. Among those, only the complexes of oxidative phosphorylation (OXPHOS) affected the CL composition. Rather than any specific complex, it was the global impairment of the OXPHOS system that altered CL and at the same time shortened its half-life. The knockdown of OXPHOS expression had the same effect on CL as the knockdown of tafazzin in Drosophila flight muscles, including a change in CL composition and the accumulation of monolyso-CL. Thus, the assembly of OXPHOS complexes induces CL remodeling, which, in turn, leads to CL stabilization. We hypothesize that protein crowding in the OXPHOS system imposes packing stress on the lipid bilayer, which is relieved by CL remodeling to form tightly packed lipid–protein complexes.

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“…Assays were performed as in ref. 71 . Mitochondria were purified from ten thoraces of 7-10-day-old male flies and BN-PAGE was performed using NativePAGE gels from Life Technologies, following the manufacturer's instructions.…”

Section: Uas-crispr Line Constructionmentioning

confidence: 99%

Circadian regulation of mitochondrial uncoupling and lifespan

et al. 2020

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Because old age is associated with defects in circadian rhythm, loss of circadian regulation is thought to be pathogenic and contribute to mortality. We show instead that loss of specific circadian clock components Period (Per) and Timeless (Tim) in male Drosophila significantly extends lifespan. This lifespan extension is not mediated by canonical diet-restriction longevity pathways but is due to altered cellular respiration via increased mitochondrial uncoupling. Lifespan extension of per mutants depends on mitochondrial uncoupling in the intestine. Moreover, upregulated uncoupling protein UCP4C in intestinal stem cells and enteroblasts is sufficient to extend lifespan and preserve proliferative homeostasis in the gut with age. Consistent with inducing a metabolic state that prevents overproliferation, mitochondrial uncoupling drugs also extend lifespan and inhibit intestinal stem cell overproliferation due to aging or even tumorigenesis. These results demonstrate that circadianregulated intestinal mitochondrial uncoupling controls longevity in Drosophila and suggest a new potential anti-aging therapeutic target.

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Regulation of Mitochondrial Complex I Biogenesis in Drosophila Flight Muscles

Cited by 62 publications

References 39 publications

Protein composition of the muscle mitochondrial reticulum during postnatal development

Protein composition of the muscle mitochondrial reticulum during postnatal development

Assembly of the complexes of oxidative phosphorylation triggers the remodeling of cardiolipin

Circadian regulation of mitochondrial uncoupling and lifespan

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