Biology subjects

Ouzounidis, V. R.

Publications and source records attributed to Ouzounidis, V. R..

2 recordsLinked to original sources

bioRxiv2024

An NADH-controlled gatekeeper of ATP synthase

ATP fuels crucial cellular processes and is obtained mostly by oxidative phosphorylation (OXPHOS) at the inner mitochondrial membrane. While significant progress has been made in mechanistic understanding of ATP production, critical aspects surrounding its substrate supply logistics are poorly understood. We identify an interaction between mitochondrial apoptosis-inducing factor 1 (AIFM1) and adenylate kinase 2 (AK2) as gatekeeper of ATP synthase. This interaction is NADH-dependent and influenced by glycolysis, linking it to the cells metabolic state. Genetic interference with AIFM1/AK2 association impedes the ability of Caenorhabditis elegans animals to handle altered metabolic rates and nutrient availability. Together, the results imply AIFM1 as a cellular NADH sensor, placing AK2 next to the OXPHOS complexes for local ADP regeneration as the substrate for ATP synthesis. This metabolic signal relay balances ATP synthase substrate supply against ATP conservation, enabling cells to adapt to fluctuating energy availability, with possible implications for AIFM1-related mitochondrial diseases. HighlightsO_LIDiscovery of AIFM1/AK2 interaction as a gatekeeper of mitochondrial ATP synthase C_LIO_LIAIFM1/AK2 interaction is NADH-dependent and linked to the cells metabolic state C_LIO_LIDisrupting AIFM1/AK2 impairs metabolic adaptation in Caenorhabditis elegans C_LIO_LIAIFM1 as NADH sensor, influencing ATP synthesis with mitochondrial disease implications C_LI

biochemistry↗

bioRxiv2024

The Outer Kinetochore Proteins KNL-1 and Ndc80 complex are Required to Pattern the Central Nervous System

The KMN (Knl1/Mis12/Ndc80) network at the kinetochore, primarily known for its role in chromosome segregation, has been shown to be repurposed during neurodevelopment. Here, we investigate the underlying neuronal mechanism and show that the KMN network is essential to establish the proper axonal organization within the C. elegans head nervous system. Post-mitotic degradation of KNL-1, which acts as a scaffold for signaling and has microtubule-binding activities at the kinetochore, led to disorganized ganglia and aberrant placement and organization of axons in the nerve ring - an interconnected axonal network. Through gene-replacement approaches, we demonstrate that the signaling motifs within KNL-1, responsible for recruiting the protein phosphatase 1, and activating the spindle assembly checkpoint are required for neurodevelopment. Interestingly, while the microtubule-binding activity is crucial to KMNs neuronal function, microtubule dynamics and organization were unaffected in the absence of KNL-1. Instead, the NDC-80 microtubule-binding mutant displayed notable defects in axon bundling during nerve ring formation, indicating its role in facilitating axon-axon contacts. Overall, these findings provide evidence for a non-canonical role for the KMN network in shaping the structure and connectivity of the nervous system in C. elegans during brain development.

cell biology↗