Biology subjects

Senoo, N.

Publications and source records attributed to Senoo, N..

4 recordsLinked to original sources

bioRxiv2025

Disturbed mitochondrial maturation in cardiolipin remodeling-deficient cardiomyocytes

Barth syndrome, a rare X-linked genetic disorder, features early-onset cardiomyopathy. The causal gene, TAFAZZIN, encodes a transacylase that mediates acyl chain remodeling of cardiolipin, a critical phospholipid in the inner mitochondrial membrane. While Barth syndrome exhibits hallmark cardiolipin abnormalities, the precise mechanisms linking TAFAZZIN deficiency and disturbed cardiolipin metabolism to progressive cardiac dysfunction remain unclear. In this study, we modeled Barth syndrome cardiomyopathy in human induced pluripotent stem cell-derived cardiomyocytes with in vitro maturation treatments that simulate heart developmental stimuli. We found that cardiomyocyte maturation involves progressive cristae dynamics associated with protein and lipid alterations in the inner mitochondrial membrane. TAFAZZIN-deficient cardiomyocytes fail to adapt to the developmental stimuli, resulting in damaged cristae, compromised mitochondrial respiration, and cardiomyocyte dysfunction. These results demonstrate that TAFAZZIN deficiency perturbs functional and structural development of mitochondria, which may contribute to mitochondrial dysfunction and associated childhood progression to cardiomyopathy in Barth syndrome.

developmental biology↗

bioRxiv2024

Self-organized acoustic behavior in bats arises from simple rules

Although self-organized behavior has been extensively studied in the movement of group-behaving animals, such as fish or birds, far less attention has been paid to vocal behavior in animal groups, especially in mammals. Here, by testing the vocal response of echolocating bats (Miniopterus fuliginosus) to the playback of jamming stimuli in the lab, we discovered a mathematical model that can well describe vocal frequency control by bats in response to jamming stimuli mimicking echolocation sounds emitted in a group of bats. We then extended the model to a group of flying bats and observed frequency-adjusting behavior by which the frequency differences for the group increased overall, similar to a previous observation on group-flying bats. Further, we showed the frequency-adjusting behavior led to less potential misdetections by echolocation in a group. Our findings suggest this frequency-adjusting behavior is a self-organized vocal behavior that mitigates conflicts within a group, one achieved via simple behavioral rules, as in other types of collective animal behavior.

animal behavior and cognition↗

bioRxiv2023

Conserved cardiolipin-mitochondrial ADP/ATP carrier interactions assume distinct structural and functional roles that are clinically relevant

The mitochondrial phospholipid cardiolipin (CL) promotes bioenergetics via oxidative phosphorylation (OXPHOS). Three tightly bound CLs are evolutionarily conserved in the ADP/ATP carrier (AAC in yeast; adenine nucleotide translocator, ANT in mammals) which resides in the inner mitochondrial membrane and exchanges ADP and ATP to enable OXPHOS. Here, we investigated the role of these buried CLs in the carrier using yeast Aac2 as a model. We introduced negatively charged mutations into each CL-binding site of Aac2 to disrupt the CL interactions via electrostatic repulsion. While all mutations disturbing the CL-protein interaction destabilized Aac2 monomeric structure, transport activity was impaired in a pocket-specific manner. Finally, we determined that a disease-associated missense mutation in one CL-binding site in ANT1 compromised its structure and transport activity, resulting in OXPHOS defects. Our findings highlight the conserved significance of CL in AAC/ANT structure and function, directly tied to specific lipid-protein interactions.

biochemistry↗

bioRxiv2022

APOE Expression and Secretion are Modulated by Copper-Dependent and -Independent Mitochondrial Dysfunction

Mitochondria influence cellular function through both cell-autonomous and non-cell autonomous mechanisms, such as production of paracrine and endocrine factors. Here, we demonstrate that mitochondrial regulation of the secretome is more extensive than previously appreciated, as both genetic and pharmacological disruption of the electron transport chain caused upregulation of the Alzheimers disease risk factor apolipoprotein E (APOE) and other secretome components. This upregulation of secretory proteins was of a similar extent as modifications to the mitochondrial annotated proteome. Indirect disruption of the electron transport chain by gene editing of SLC25A mitochondrial membrane transporters as well as direct genetic and pharmacological disruption of either complexes I, III, or the copper-containing complex IV of the electron transport chain, elicited upregulation of APOE transcript, protein, and secretion, up to 49-fold. These APOE phenotypes were robustly expressed in diverse cell types and iPSC-derived human astrocytes as part of an inflammatory gene expression program. Moreover, age- and genotype-dependent decline in brain levels of respiratory complex I preceded an increase in APOE in the 5xFAD mouse model. We propose that mitochondria act as novel upstream regulators of APOE-dependent cellular processes in health and disease.

cell biology↗