European Companies Search Engine
UK funding (£730,677): Form and function of the mitochondrial sites of contact with the nucleus Ukri1 Nov 2024 UK Research and Innovation, United Kingdom
Overview
Text
Form and function of the mitochondrial sites of contact with the nucleus
| Abstract | Membrane contact sites (MCS) define communication between intracellular organelles functioning both as connectors and checkpoints. The MCS's role in the preservation of cellular homeostasis is now vastly accepted increasing the attention to the repertoire of molecules governing their function to inform biological mechanisms underpinning diseases. Thus, compromised MCS between organelles lead to corrupted cell signalling which ensues in pathological onset. Recently, the presence of MCS between mitochondria and the nucleus has been uncovered in mammalian cells by our group. Called Nucleus Associated Mitochondria (NAM) these newly identified MCS are proposed to prime the expression of genes required for cellular resistance to stressors by ensuring a tethering mechanism for homeostatic intracellular communication. Mitochondria are paramount to cellular homeostasis and influenced by the interplay between anabolic and catabolic processes of preservation. Loss of mitochondrial integrity triggers pathological reprogramming whereby the redesigned bio-energetic routes cause cellular and systemic damage. Defective mitochondria are nonetheless resilient and promptly relay with the nucleus to stimulate or repress the expression of genes which protect cellular integrity. This process is termed Mitochondrial Retrograde Response (MRR) and dictates the degree of cellular adaptation to stress. This is part of the bidirectional interplay between the nucleus and mitochondria: the anterograde one which goes from the nucleus to mitochondria to empower biogenesis (i) and the retrograde which travels in the opposite direction to prime the genome (ii). NAM concur with the efficiency of the MRR by forming physical contacts which expedite the adaptation of the nucleus to mitochondrial priming. The characterization of the tethering mechanism at the basis of the NAM may therefore enlighten the hierarchy between signalling and genetics both in physiology and pathology. Based on these premises, we hypothesise that contacts between mitochondria and the nucleus rely on a repertoire of molecules (i) that establish a dynamic tether to command signalling and metabolism (ii), shaping genetic and epigenetic profiles in mammalian cells (iii). We shall test this by achieving the following experimental aims: I. Identify the molecules composing and regulating the NAM tethering complex; II. Assess cell signaling and mitochondrial-nuclear metabolic crosstalk in NAM-modulated cells; III. Appraise the role of NAM in genetic and epigenetic reprogramming. The proposed experimental plan will utilise state-of-the-art techniques of biochemical, metabolic, and signalling analysis along with multi-omics approaches to provide proof that the physical interaction between mitochondria and the nucleus is instrumental for successful and integrated cell signalling at the basis of functional homeostasis. The team assembled to complete the experimental plan holds the expertise and ambition to inform on these hidden aspects of cellular communication by revealing a regulatory axis which determines the homeostasis of mammalian cells. A timely and innovative effort which will deliver impact at multiple levels starting with first-in-class training for early career researchers in one of the fast-growing fields of experimental biomedicine. |
| Category | Research and Innovation |
| Reference | BB/Z516417/1 |
| Status | Active |
| Funded period start | 01/11/2024 |
| Funded period end | 31/10/2027 |
| Funded value | £730,677.00 |
| Source | https://gtr.ukri.org/projects?ref=BB%2FZ516417%2F1 |
Participating Organisations
| Queen Mary University of London |
The filing refers to a past date, and does not necessarily reflect the current state. The current state is available on the following page: Queen Mary University of London, London.
The visualizations for "Queen Mary University of London - UK funding (£730,677): Form and function of the mitochondrial sites of contact with the nucleus"
are provided by
North Data
and may be reused under the terms of the
Creative Commons CC-BY license.
