A Sideroflexin/Connexin adaptor ties kinesin-3 to mitochondria in neurons DOI Creative Commons
Syed Nooruzuha Barmaver, Oliver I. Wagner

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: June 9, 2023

Abstract We identified SFXN-1.2 to regulate both morphologies as well dynamics of mitochondria. is an ortholog human Sideroflexin 1/3 associated with Alzheimer's and Parkinson's disease. show that binds kinesin-3 KIF1A(UNC-104) via CX32 (Connexin 32), a protein known be linked Charcot-Marie-Tooth diseases. While affect the mitochondria, they also motility molecular motor UNC-104 alone. found no role motor's PH domain in linking has effect on synaptic vesicle trafficking underlining specificity its mitochondria transport. narrowed down critical interaction schemes UNC-104/CX32/SFXN-1.2 complex. Strikingly, mutations lead motor- sensory neuron defects C. elegans affecting animal's touch responses restricting body movements. Lastly, we revealed neither mitochondrial bioenergetics nor mitophagy are affected by sfxn-1.2 mutation.

Language: Английский

Mitochondria in Mesenchymal Stem Cells: Key to Fate Determination and Therapeutic Potential DOI
Yang Liu, Lingjuan Wang, Jihui Ai

et al.

Stem Cell Reviews and Reports, Journal Year: 2024, Volume and Issue: 20(3), P. 617 - 636

Published: Jan. 24, 2024

Language: Английский

Citations

6
Corneal epithelial cells upregulate macropinocytosis to engulf metabolically active axonal mitochondria released by injured axons DOI Creative Commons

Sonali Pal‐Ghosh,

Himani Datta-Majumdar,

Shyamali Datta

et al.

The Ocular Surface, Journal Year: 2025, Volume and Issue: 37, P. 173 - 188

Published: April 7, 2025

To determine the mechanisms used to internalize mitochondria by corneal epithelial cells after in vivo trephine injury and vitro cells. Male female mice were subjected euthanized immediately, 6, 24 hours injury. Macropinocytosis was quantified using 70 kD fluorescent dextran. Mitochondrial content assessed immunofluorescence metabolic activity Seahorse assay immediately 6 In experiments human limbal (HCLE) isolated performed assess mitochondrial transfer presence of gap junction inhibitor 18α-glycyrrhetinc acid macropincytosis ethylisopropylamiloride. Mitochondria accumulate within apical cell layers minutes also increases Oxygen Consumption Rates increase epithelium males females. Inhibiting junctions engulfment while inhibiting macropinocytosis prevents vitro. Molecules released injured severed axons induce An oxygen consumption rate indicates that axonal can evade lysosomal degradation for at least hours. studies labeled unlabeled control mechanically stressed confirm involvement free vesicle bound

Language: Английский

Citations

0
Developmental deletion of amyloid precursor protein precludes transcriptional and proteomic responses to brain injury DOI Creative Commons
Valentina Lacovich, Mária Čarná,

Sebastian J. Novotný

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(4)

Published: April 1, 2025

Abstract INTRODUCTION Amyloid precursor protein (APP) undergoes striking changes following traumatic brain injury (TBI). Considering its role in the control of gene expression, we investigated whether APP regulates transcription and translation TBI. METHODS We assessed morphology ( n = 4–9 mice/group), transcriptome 3 proteome behavior 17–27 mice/group) wild‐type (WT) knock‐out (KO) mice either untreated or 10‐weeks RESULTS After TBI, WT displayed transcriptional programs consistent with late stages repair, hub genes were predicted to impact showed subtle changes. KO largely replicated this repertoire, but no nor translational response DISCUSSION The similarities between TBI suggest that developmental deficiency induces a condition reminiscent hampering expression injury. Highlights after brains exhibit profiles stage repair. Developmental maintains perpetually an immature state akin responds by at level. precludes molecular

Language: Английский

Citations

0
Effect of Dietary Phospholipid on the Behavior in C57BL/6J Mice DOI
Lidiya V. Boldyreva, Maryana V. Morozova, Konstantin S. Pavlov

et al.

Journal of Evolutionary Biochemistry and Physiology, Journal Year: 2024, Volume and Issue: 60(1), P. 409 - 419

Published: Jan. 1, 2024

Language: Английский

Citations

2
Three-dimensional ultrastructure analysis of organelles in injured motor neuron DOI Creative Commons
Hiromi Tamada

Anatomical Science International, Journal Year: 2023, Volume and Issue: 98(3), P. 360 - 369

Published: April 18, 2023

Morphological analysis of organelles is one the important clues for understanding cellular conditions and mechanisms occurring in cells. In particular, nanoscale information within crowded intracellular tissues provide more direct implications when compared to analyses cells culture or isolation. However, there are some difficulties detecting individual shape using light microscopy, including super-resolution microscopy. Transmission electron microscopy (TEM), wherein ultrastructure can be imaged at membrane level, cannot determine whole structure, analyze it quantitatively. Volume EM, such as focused ion beam/scanning (FIB/SEM), a powerful tool explore details three-dimensional ultrastructures even certain volume, measure several parameters from them. this review, advantages FIB/SEM organelle studies highlighted along with introduction mitochondrial injured motor neurons. This would aid morphological mitochondria, especially those distributed cell bodies well axon initial segment (AIS) mouse tissues. These regions have not been explored thus far due encountered accessing their images by conditional microscopies. Some nerve regeneration also discussed reference obtained findings. Finally, future perspectives on introduced. The combination biochemical genetic structures distribution morphology will help match achievements genomics structural biology.

Language: Английский

Citations

4
p17/C18-ceramide–mediated mitophagy is an endogenous neuroprotective response in preclinical and clinical brain injury DOI Creative Commons
Eda Karakaya, Natalia Oleinik, Jazlyn Edwards

et al.

PNAS Nexus, Journal Year: 2024, Volume and Issue: 3(2)

Published: Feb. 1, 2024

Abstract Repeat concussions (or repetitive mild traumatic brain injury [rmTBI]) are complex pathological processes consisting of a primary insult and long-term secondary complications also prerequisite for chronic encephalopathy (CTE). Recent evidence implies significant role autophagy-mediated dysfunctional mitochondrial clearance, mitophagy, in the cascade deleterious events resulting from TBI. C18-ceramide, bioactive sphingolipid produced response to cell stress damage, its synthesizing enzyme (CerS1) precursors selective stress-mediated mitophagy. A transporter, p17, mediates trafficking CerS1, induces C18-ceramide synthesis membrane, acts as an elimination signal survival. Whether p17-mediated mitophagy occurs plays causal quality control disease development after rmTBI unknown. Using novel less-than-mild TBI (rlmTBI) paradigm, ablation p17/C18-ceramide p17 knockout (KO) mice results loss C18-ceramide–induced which contributes susceptibility recovery associated with rlmTBI. ceramide analog lipid-selenium conjugate drug, LCL768 restored reduced complications, improving cognitive deficits rlmTBI-induced p17KO mice. We obtained reduction expression considerable decrease CerS1 levels cortical mitochondria CTE human brains compared age-matched brains. These data demonstrated that is endogenous neuroprotective following rlmTBI, thus suggesting prospective strategy interrupt consequences concussive

Language: Английский

Citations

1
Neuronal toxicity and recovery from early bortezomib-induced neuropathy: targeting the blood nerve barrier but not the dorsal root ganglion DOI Open Access

Mariam Sobhy Atalla,

Anna-Lena Bettenhausen,

Julius M. Verse

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Abstract The use of the first in class proteasome inhibitor Bortezomib (BTZ) is highly effective treatment multiple myeloma. However, it’s long-term limited by fact, that most treated patients develop dose limiting painful polyneuropathy. In some patients, pain resolves after variable timeframes, others it persists, despite discontinuation treatment, with underlying mechanisms poorly understood. One condition neural toxicity ability to penetrate blood nerve barrier. Here we present pathways involved early bortezomib-induced polyneuropathy (BIPN) development and its resolution, rats myeloma patients. cycle BTZ elicited transient mechanical hyperalgesia cold allodynia rats. Transcriptomic signature network analysis revealed regulation circadian, extracellular matrix, immune genes within modest changes dorsal root ganglia. Recovery processes resealed small molecule leakiness perineurial barrier, reversed axonal swelling, normalized fiber density skin. Expression microtubule-associated cytoskeletal protein cortactin matched this process perineurium. Netrin-1 (Ntn1) as a known barrier sealer was also upregulated resolution BIPN skin NTN1 independent damage. summary, our data demonstrate targets mainly indicates could be supported protective growth factors like Ntn1 for remodeling matrix neuronal barriers. Summary leads dose-limiting Already cycle, weakens which reseals upon upregulation netrin-1.

Language: Английский

Citations

1
Axonal mitophagy in retinal ganglion cells DOI Creative Commons
Liang Yang,

Yulin Li,

Qing Jiao

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 29, 2024

Neurons, exhibiting unique polarized structures, rely primarily on the mitochondrial production of ATP to maintain their hypermetabolic energy requirements. To a normal supply, mitochondria are transported distal end axon. When within axon critically damaged beyond compensatory capacity, they cleared via autophagosomal phagocytosis, and degradation products recycled replenish energy. dysfunctional or transport processes blocked, axons become susceptible degeneration triggered by depletion, resulting in neurodegenerative diseases. As final checkpoint for quality control, axonal mitophagy is vital neuronal growth, development, injury, regeneration. Furthermore, abnormal crucial pathogenesis optic nerve-related diseases such as glaucoma. We review recent studies summarize progress research provide insights into associated with damage ganglion cells.

Language: Английский

Citations

1
Effect of dietary phospholipid on the behavior in C57BL/6J mice DOI
Lidiya V. Boldyreva, Maryana V. Morozova, Konstantin S. Pavlov

et al.

Российский физиологический журнал им  И  М  Сеченова, Journal Year: 2024, Volume and Issue: 110(2), P. 254 - 267

Published: Aug. 2, 2024

Nowadays phospholipids are widely used as hepatoprotective, neuroprotective and anti-stress drugs, well the dietary supplements. Besides, lecithin consisting up to 70% of mixture: phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol phosphatidic acid, is often component food production an emulsifier. Dose these biologically active substances in modern human diet could be quite high. Previously we have shown that chronic intestinal inflammation Muc2-knockout mice induces behavioral changes along with significant increase content epithelial cells, particularly, phosphatidylserine acid. Here investigate effects long-term administration a mixture phospholipids, soy on patterns laboratory mice. Animals taken phospholipid shows no normally observed preference towards females two intruders test (with female male). In social odor test, they also did not distinguish male odors, while non-social odors discrimination preserved. addition, identified decrease anxiety, obsessive traits, schizophrenia-like behavior traits animals. Soy supplementation had similar compulsive increased aggression males. Thus, perinatal either (phosphatidylcholine, acid) or can influence various aspects

Language: Английский

Citations

0
A Sideroflexin/Connexin adaptor ties kinesin-3 to mitochondria in neurons DOI
Syed Nooruzuha Barmaver, Odvogmed Bayansan,

Muhammad Safwan Khawaja

et al.

Published: Oct. 17, 2024

Abstract Various neurological diseases are linked to changes in mitochondrial trafficking axons. Thus, it is crucial understand how dynamics of mitochondria regulated on the molecular level. From a candidate screen, we identified SFXN-1.2 regulate both morphologies as well mitochondria. an ortholog human Sideroflexin 1/3 associated with Alzheimer's disease and Parkinson's diseases. We demonstrate that binds kinesin-3 KIF1A(UNC-104) via CX32 (Connexin 32 or GJB1), protein known be Charcot-Marie-Tooth disease. While affect mitochondria, they also motility motor UNC-104 alone. yeast two-hybrid, co-immunoprecipitation bimolecular fluorescent complementation assays, narrowed down critical interaction schemes UNC-104/CX32/SFXN-1.2 complex. Interestingly, though synaptic vesicles its PH domain, found no role this domain linking Strikingly, mutations lead motor- sensory neuron defects C. elegans negatively affecting animal's touch responses restricting body movements. Lastly, neither bioenergetics nor mitophagy affected by sfxn-1.2 mutations.

Language: Английский

Citations

0