Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Gottschalk, B; Koshenov, Z; Malli, R; Graier, WF.
Implications of mitochondrial membrane potential gradients on signaling and ATP production analyzed by correlative multi-parameter microscopy.
Sci Rep. 2024; 14(1): 14784
Doi: 10.1038/s41598-024-65595-z
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- Führende Autor*innen der Med Uni Graz
- Gottschalk Benjamin
- Graier Wolfgang
- Co-Autor*innen der Med Uni Graz
- Koshenov Zhanat
- Malli Roland
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- Abstract:
- The complex architecture and biochemistry of the inner mitochondrial membrane generate ultra-structures with different phospholipid and protein compositions, shapes, characteristics, and functions. The crista junction (CJ) serves as an important barrier separating the cristae (CM) and inner boundary membranes (IBM). Thereby CJ regulates the movement of ions and ensures distinct electrical potentials across the cristae (ΔΨC) and inner boundary (ΔΨIBM) membranes. We have developed a robust and flexible approach to visualize the CJ permeability with super-resolution microscopy as a readout of local mitochondrial membrane potential (ΔΨmito) fluctuations. This method involves analyzing the distribution of TMRM fluorescence intensity in a model that is restricted to the mitochondrial geometry. We show that mitochondrial Ca2+ elevation hyperpolarizes the CM most likely caused by Ca2+ sensitive increase of mitochondrial tricarboxylic acid cycle (TCA) and subsequent oxidative phosphorylation (OXPHOS) activity in the cristae. Dynamic multi-parameter correlation measurements of spatial mitochondrial membrane potential gradients, ATP levels, and mitochondrial morphometrics revealed a CJ-based membrane potential overflow valve mechanism protecting the mitochondrial integrity during excessive cristae hyperpolarization.
- Find related publications in this database (using NLM MeSH Indexing)
- Membrane Potential, Mitochondrial - physiology
- Adenosine Triphosphate - metabolism
- Animals - administration & dosage
- Mitochondrial Membranes - metabolism
- Signal Transduction - administration & dosage
- Oxidative Phosphorylation - administration & dosage
- Calcium - metabolism
- Mitochondria - metabolism
- Microscopy - methods
- Humans - administration & dosage
- Find related publications in this database (Keywords)
- Mitochondria
- Mitochondrial membranes
- Cristae junctions
- Membrane potential gradient
- Correlative microscopy