Persistent luminescence (PersL) imaging without real-time external excitation has been regarded as the next generation of autofluorescence-free optical imaging technology. However, to achieve ...improved imaging resolution and deep tissue penetration, developing new near-infrared (NIR) persistent phosphors with intense and long duration PersL over 1000 nm is still a challenging but urgent task in this field. Herein, making use of the persistent energy transfer process from Cr3+ to Er3+, we report a novel garnet persistent phosphor of Y3Al2Ga3O12 codoped with Er3+ and Cr3+ (YAGG:Er–Cr), which shows intense Cr3+ PersL (∼690 nm) in the deep red region matching well with the first biological window (NIR-I, 650–950 nm) and Er3+ PersL (∼1532 nm) in the NIR region matching well with the third biological window (NIR-III, 1500–1800 nm). The optical imaging through raw-pork tissues (thickness of 1 cm) suggests that the emission band of Er3+ can achieve higher spatial resolution and more accurate signal location than that of Cr3+ due to the reduced light scattering at longer wavelengths. Furthermore, by utilizing two independent electron traps with two different trap depths in YAGG:Er–Cr, the Cr3+/Er3+ PersL can even be recharged in situ by photostimulation with 660 nm LED thanks to the redistribution of trapped electrons from the deep trap to the shallow one. Our results serve as a guide in developing promising NIR (>1000 nm) persistent phosphors for long-term optical imaging.
The mitochondrion is an essential organelle for a wide range of cellular processes, including energy production, metabolism, signal transduction and cell death. To execute these functions, ...mitochondria regulate their size, number, morphology and distribution in cells via mitochondrial division and fusion. In addition, mitochondrial division and fusion control the autophagic degradation of dysfunctional mitochondria to maintain a healthy population. Defects in these dynamic membrane processes are linked to many human diseases that include metabolic syndrome, myopathy and neurodegenerative disorders. In the last several years, our fundamental understanding of mitochondrial fusion, division and degradation has been significantly advanced by high resolution structural analyses, protein-lipid biochemistry, super resolution microscopy and in vivo analyses using animal models. Here, we summarize and discuss this exciting recent progress in the mechanism and function of mitochondrial division and fusion.
It is unknown what occurs if both mitochondrial division and fusion are completely blocked. Here, we introduced mitochondrial stasis by deleting two dynamin-related GTPases for division (Drp1) and ...fusion (Opa1) in livers. Mitochondrial stasis rescues liver damage and hypotrophy caused by the single knockout (KO). At the cellular level, mitochondrial stasis re-establishes mitochondrial size and rescues mitophagy defects caused by division deficiency. Using Drp1KO livers, we found that the autophagy adaptor protein p62/sequestosome-1—which is thought to function downstream of ubiquitination—promotes mitochondrial ubiquitination. p62 recruits two subunits of a cullin-RING ubiquitin E3 ligase complex, Keap1 and Rbx1, to mitochondria. Resembling Drp1KO, diet-induced nonalcoholic fatty livers enlarge mitochondria and accumulate mitophagy intermediates. Resembling Drp1Opa1KO, Opa1KO rescues liver damage in this disease model. Our data provide a new concept that mitochondrial stasis leads the spatial dimension of mitochondria to a stationary equilibrium and a new mechanism for mitochondrial ubiquitination in mitophagy.
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•Balanced mitochondrial dynamics are important for liver health•p62-Keap1-Rbx1 complex ubiquitinates mitochondria in parkin-independent mitophagy•Fatty livers generate megamitochondria and block parkin-independent mitophagy•Suppressing megamitochondria formation by Opa1KO rescues damage in fatty livers
Yamada et al. show that mitochondrial size is antagonistically regulated by division and fusion and that extreme mitochondrial size is deleterious in the liver. They identify a new parkin-independent mitophagy pathway, which is inhibited by megamitochondria present in nonalcoholic liver hepatocytes. Restoring mitophagy could be beneficial in NAFLD.
The properties of 322 intermediate-mass late-G giants (comprising 10 planet-host stars) selected as the targets of the Okayama Planet Search Program, many of which are red-clump giants, were ...comprehensively investigated by establishing their various stellar parameters (atmospheric parameters, including turbulent velocity fields, metallicity, luminosity, mass, age, projected rotational velocity, etc.), and their photospheric chemical abundances for 17 elements, in order to study their mutual dependence, connection with the existence of planets, and possible evolution-related characteristics. The metallicity distribution of planet-host giants was found to be almost the same as that of non-planet-host giants, making marked contrast to the case of planet-host dwarfs tending to be metal-rich. Generally, the metallicities of these comparatively young (typical age of
$\sim 10^{9}$
yr) giants tend to be somewhat lower than those of dwarfs at the same age, and super-metal-rich (Fe
$/$
H
$\gt$
0.2) giants appear to be lacking. Apparent correlations were found between the abundances of C, O, and Na, suggesting that the surface compositions of these elements have undergone appreciable changes due to dredge-up of H-burning products by evolution-induced deep envelope mixing, which becomes more efficient for higher mass stars.
Mitochondria are highly dynamic organelles that continuously grow, divide, and fuse. The division of mitochondria is crucial for human health. During mitochondrial division, the mechano-guanosine ...triphosphatase (GTPase) dynamin-related protein (Drp1) severs mitochondria at endoplasmic reticulum (ER)-mitochondria contact sites, where peripheral ER tubules interact with mitochondria. Here, we report that Drp1 directly shapes peripheral ER tubules in human and mouse cells. This ER-shaping activity is independent of GTP hydrolysis and located in a highly conserved peptide of 18 amino acids (termed D-octadecapeptide), which is predicted to form an amphipathic α helix. Synthetic D-octadecapeptide tubulates liposomes in vitro and the ER in cells. ER tubules formed by Drp1 promote mitochondrial division by facilitating ER-mitochondria interactions. Thus, Drp1 functions as a two-in-one protein during mitochondrial division, with ER tubulation and mechano-GTPase activities.
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•Drp1 is associated with the ER•Drp1 shapes the ER into tubules independently of oligomerization and GTP hydrolysis•Octadecapeptide554–571 in the variable domain is sufficient for membrane tubulation•ER tubules formed by Drp1 promote mitochondrial division
Adachi et al. report that Drp1 shapes the ER into tubules independently of GTP hydrolysis. ER tubules formed by Drp1 promote mitochondrial division by facilitating ER-mitochondria interactions. Thus, Drp1 functions as a two-in-one protein during mitochondrial division, with ER tubulation and mechano-GTPase activities.
Stem cells divide and undergo self-renewal depending on the signals received from the stem cell niche. This phenomenon is indispensable to maintain tissues and organs in individuals. However, not all ...the molecular factors and mechanisms of self-renewal are known. In our previous study, we reported that glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) synthesized in the distal tip cells (DTCs; the stem cell niche) are essential for germline stem cell proliferation in Caenorhabditis elegans. Here, we characterized the GPI-APs required for proliferation. We selected and verified the candidate GPI-APs synthesized in DTCs by RNA interference screening and found that F57F4.3 (GFI-1), F57F4.4 and F54E2.1 are necessary for germline proliferation. These proteins are likely involved in the same pathway for proliferation and activated by the transcription factor PQM-1. We further provided evidence suggesting that these GPI-APs act through fatty acid remodelling of the GPI anchor, which is essential for association with lipid rafts. These findings demonstrated that GPI-APs, particularly F57F4.3/4 and F54E2.1, synthesized in the germline stem cell niche are located in lipid rafts and involved in promoting germline stem cell proliferation in C. elegans. The findings may thus shed light on the mechanisms by which GPI-APs regulate stem cell self-renewal.
We have developed a novel persistent phosphor of LaAlO
3
perovskite doped with Er
3+
, Cr
3+
, and Sm
3+
(LAO:Er-Cr-Sm), which exhibits long persistent luminescence (PersL) at 1553 nm due to the Er
...3+
:
4
I
13/2
→
4
I
15/2
transition as well as at 734 nm due to the Cr
3+
:
2
E(
2
G) →
4
A
2
(
4
F) transition. The intense near-infrared (NIR) PersL bands from Cr
3+
and Er
3+
match well with the first (NIR-I, 650-950 nm) and third (NIR-III, 1500-1800 nm) biological windows as well as response curves of commercial Si and InGaAs detectors. The photon emission rates of Cr
3+
(6.06 × 10
16
cps sr
−1
m
−2
) and Er
3+
(3.69 × 10
16
cps sr
−1
m
−2
) at 60 min after ceasing ultraviolet (UV) illumination were comparable with that of the widely used ZnGa
2
O
4
:Cr
3+
red persistent phosphor (5.41 × 10
16
cps sr
−1
m
−2
). Furthermore, we also show the first
in vitro
autofluorescence-free imaging through pork tissues by Si/InGaAs cameras monitoring Cr
3+
/Er
3+
PersL, and demonstrate that the Er
3+
emission can achieve higher spatial resolution than the Cr
3+
emission due to the reduced light scattering at longer wavelengths. It is indicated that this material can act as a promising bio-probe for
in vivo
optical imaging, especially in the NIR-III biological window.
We have developed a novel persistent phosphor of LaAlO
3
perovskite doped with Er
3+
, Cr
3+
and Sm
3+
(LAO:Er-Cr-Sm), which exhibits long persistent luminescence (PersL) at 1553 nm due to the Er
3+
:
4
I
13/2
→
4
I
15/2
transition as well as at 734 nm due to the Cr
3+
:
2
E(
2
G) →
4
A
2
(
4
F) transition.
Dynamin-related protein 1 (Drp1) divides mitochondria as a mechano-chemical GTPase. However, the function of Drp1 beyond mitochondrial division is largely unknown. Multiple Drp1 isoforms are produced ...through mRNA splicing. One such isoform, Drp1
, contains all four alternative exons and is specifically expressed in the brain. Here, we studied the function of Drp1
in mouse neurons in both culture and animal systems using isoform-specific knockdown by shRNA and isoform-specific knockout by CRISPR/Cas9. We found that the expression of Drp1
is induced during postnatal brain development. Drp1
is enriched in dendritic spines and regulates postsynaptic clathrin-mediated endocytosis by positioning the endocytic zone at the postsynaptic density, independently of mitochondrial division. Drp1
loss promotes the formation of ectopic dendrites in neurons and enhanced sensorimotor gating behavior in mice. These data reveal that Drp1
controls postsynaptic endocytosis, neuronal morphology and brain function.
The human mtHSP60/HSPD1-mtHSP10/HSPE1 system prevents protein misfolding and maintains proteostasis in the mitochondrial matrix. Altered activities of this chaperonin system have been implicated in ...human diseases, such as cancer and neurodegeneration. However, how defects in HSPD1 and HSPE1 affect mitochondrial structure and dynamics remains elusive. In the current study, we address this fundamental question in a human cell line, HEK293T. We found that the depletion of HSPD1 or HSPE1 results in fragmentation of mitochondria, suggesting a decrease in mitochondrial fusion. Supporting this notion, HSPE1 depletion led to proteolytic inactivation of OPA1, a dynamin-related GTPase that fuses the mitochondrial membrane. This OPA1 inactivation was mediated by a stress-activated metalloprotease, OMA1. In contrast, HSPD1 depletion did not induce OMA1 activation or OPA1 cleavage. These data suggest that HSPE1 controls mitochondrial morphology through a mechanism separate from its chaperonin activity.
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•Depletion of HSPE1 results in the cleavage of OPA1 independent of HSPD1•HSPD1 and HSPE1 depletion decreases respiration activity•OMA1 plays a role in OPA1 cleavage from HSPE1 depletion•The mobile loop region of HSPE1 is required to rescue OPA1 cleavage
Biological sciences; Molecular biology; Cell biology
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