Defective mitochondrial COX1 translation due to loss of COX14 function triggers ROS-induced inflammation in mouse liver.

Mitochondrial oxidative phosphorylation (OXPHOS) fuels cellular ATP demands. OXPHOS defects lead to severe human disorders with unexplained tissue specific pathologies. Mitochondrial gene expression is essential for OXPHOS biogenesis since core subunits of the complexes are mitochondrial-encoded.

Diabetes and Parkinson's Disease: Understanding Shared Molecular Mechanisms.

Aging is a major risk factor for Parkinson's disease (PD). Genetic mutations account for a small percentage of cases and the majority appears to be sporadic, with yet unclear causes. However, various environmental factors have been linked to an increased risk of developing PD and, therefore, understanding the complex interplay between genetic and environmental factors is crucial for developing effective disease-modifying therapies.

Amino-terminally elongated Aβ peptides are generated by the secreted metalloprotease ADAMTS4 and deposit in a subset of Alzheimer's disease brains.

Aims: The aggregation and deposition of amyloid-β (Aβ) peptides in the brain is thought to be the initial driver in the pathogenesis of Alzheimer's disease (AD). Aside from full-length Aβ peptides starting with an aspartate residue in position 1, both N-terminally truncated and elongated Aβ peptides are produced by various proteases from the amyloid precursor protein (APP) and have been detected in brain tissues and body fluids. Recently, we demonstrated that the particularly abundant N-terminally truncated Aβ4-x peptides are generated by ADAMTS4, a secreted metalloprotease that is exclusively expressed in the oligodendrocyte cell population.

Coordinating mitochondrial translation with assembly of the OXPHOS complexes.

The mitochondrial oxidative phosphorylation (OXPHOS) system produces the majority of energy required by cells. Given the mitochondrion's endosymbiotic origin, the OXPHOS machinery is still under dual genetic control where most OXPHOS subunits are encoded by the nuclear DNA and imported into mitochondria, while a small subset is encoded on the mitochondrion's own genome, the mitochondrial DNA (mtDNA). The nuclear and mtDNA encoded subunits must be expressed and assembled in a highly orchestrated fashion to form a functional OXPHOS system and meanwhile prevent the generation of any harmful assembly intermediates.

Toward Optogenetic Hearing Restoration.

The cochlear implant (CI) is considered the most successful neuroprosthesis as it enables speech comprehension in the majority of the million otherwise deaf patients. In hearing by electrical stimulation of the auditory nerve, the broad spread of current from each electrode acts as a bottleneck that limits the transfer of sound frequency information. Hence, there remains a major unmet medical need for improving the quality of hearing with CIs.

Optical measurement of glutamate release robustly reports short-term plasticity at a fast central synapse.

Introduction: Recently developed fluorescent neurotransmitter indicators have enabled direct measurements of neurotransmitter in the synaptic cleft. Precise optical measurements of neurotransmitter release may be used to make inferences about presynaptic function independent of electrophysiological measurements.

Methods: Here, we express iGluSnFR, a genetically encoded glutamate reporter in mouse spiral ganglion neurons to compare electrophysiological and optical readouts of presynaptic function and short-term synaptic plasticity at the endbulb of Held synapse.

MIC10b can polymerize into cristae-shaping filaments.

Cristae are invaginations of the mitochondrial inner membrane that are crucial for cellular energy metabolism. The formation of cristae requires the presence of a protein complex known as MICOS, which is conserved across eukaryotic species. One of the subunits of this complex, MIC10, is a transmembrane protein that supports cristae formation by oligomerization.

Devising a framework of optogenetic coding in the auditory pathway: Insights from auditory midbrain recordings.

Cochlear implants (CIs) restore activity in the deafened auditory system via electrical stimulation of the auditory nerve. As the spread of electric current in biological tissues is rather broad, the spectral information provided by electrical CIs is limited. Optogenetic stimulation of the auditory nerve has been suggested for artificial sound coding with improved spectral selectivity, as light can be conveniently confined in space.

Support for a radiation of free-living flatworms in the African Great Lakes region and the description of five new Macrostomum species.

Background: The African Great Lakes have long been recognized as an excellent location to study speciation. Most famously, cichlid fishes have radiated in Lake Tanganyika and subsequently spread into Lake Malawi and Lake Victoria, where they again radiated. Other taxa have diversified in these lakes, such as catfish, ostracods, gastropods, and Monegenean gill parasites of cichlids.

Metabolic switch from fatty acid oxidation to glycolysis in knock-in mouse model of Barth syndrome.

Mitochondria are central for cellular metabolism and energy supply. Barth syndrome (BTHS) is a severe disorder, due to dysfunction of the mitochondrial cardiolipin acyl transferase tafazzin. Altered cardiolipin remodeling affects mitochondrial inner membrane organization and function of membrane proteins such as transporters and the oxidative phosphorylation (OXPHOS) system.

More than meets the eye in Parkinson's disease and other synucleinopathies: from proteinopathy to lipidopathy.

The accumulation of proteinaceous inclusions in the brain is a common feature among neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease (PD), and dementia with Lewy bodies (DLB). The main neuropathological hallmark of PD and DLB are inclusions, known as Lewy bodies (LBs), enriched not only in α-synuclein (aSyn), but also in lipid species, organelles, membranes, and even nucleic acids. Furthermore, several genetic risk factors for PD are mutations in genes involved in lipid metabolism, such as GBA1, VSP35, or PINK1.

Cytochrome c oxidase biogenesis - from translation to early assembly of the core subunit COX1.

Mitochondria are the powerhouses of the cell as they produce the majority of ATP with their oxidative phosphorylation (OXPHOS) machinery. The OXPHOS system is composed of the F F ATP synthase and four mitochondrial respiratory chain complexes, the terminal enzyme of which is the cytochrome c oxidase (complex IV) that transfers electrons to oxygen, generating water. Complex IV comprises of 14 structural subunits of dual genetic origin: while the three core subunits are mitochondrial encoded, the remaining constituents are encoded by the nuclear genome.

A quantitative fluorescence-based approach to study mitochondrial protein import.

Mitochondria play central roles in cellular energy production and metabolism. Most proteins required to carry out these functions are synthesized in the cytosol and imported into mitochondria. A growing number of metabolic disorders arising from mitochondrial dysfunction can be traced to errors in mitochondrial protein import.

The multifaceted mitochondrial OXA insertase.

Most mitochondrial proteins are synthesized in the cytosol and transported into mitochondria by protein translocases. Yet, mitochondria contain their own genome and gene expression system, which generates proteins that are inserted in the inner membrane by the oxidase assembly (OXA) insertase. OXA contributes to targeting proteins from both genetic origins.

Cell types and synchronous-activity patterns of inspiratory neurons in the preBötzinger complex of mouse medullary slices during early postnatal development.

To examine whether and how the inspiratory neuronal network in the preBötzinger complex (preBötC) develops during the early postnatal period, we quantified the composition of the population of inspiratory neurons between postnatal day 1 (p1) and p10 by applying calcium imaging to medullary transverse slices in double-transgenic mice expressing fluorescent marker proteins. We found that putative excitatory and glycinergic neurons formed a majority of the population of inspiratory neurons, and the composition rates of these two inspiratory neurons inverted at p5-6. We also found that the activity patterns of these two types of inspiratory neurons became significantly well-synchronized with the inspiratory rhythmic bursting pattern in the preBötC within the first postnatal week.

A multimodal imaging workflow for monitoring CAR T cell therapy against solid tumor from whole-body to single-cell level.

CAR T cell research in solid tumors often lacks spatiotemporal information and therefore, there is a need for a molecular tomography to facilitate high-throughput preclinical monitoring of CAR T cells. Furthermore, a gap exists between macro- and microlevel imaging data to better assess intratumor infiltration of therapeutic cells. We addressed this challenge by combining 3D µComputer tomography bioluminescence tomography (µCT/BLT), light-sheet fluorescence microscopy (LSFM) and cyclic immunofluorescence (IF) staining.