bims-mitper 2023-06-04 papers

Sci Adv. 2023 Jun 02. 9(22): eadg7940

Creation of distinctive Bax-lipid complexes at mitochondrial membrane surfaces drives pore formation to initiate apoptosis.

Luke A Clifton, Hanna P Wacklin-Knecht, Jörgen Ådén, Ameeq Ul Mushtaq, Tobias Sparrman, Gerhard Gröbner.

Apotosis is an essential process tightly regulated by the Bcl-2 protein family where proapoptotic Bax triggers cell death by perforating the mitochondrial outer membrane. Although intensively studied, the molecular mechanism by which these proteins create apoptotic pores remains elusive. Here, we show that Bax creates pores by extracting lipids from outer mitochondrial membrane mimics by formation of Bax/lipid clusters that are deposited on the membrane surface. Time-resolved neutron reflectometry and Fourier transform infrared spectroscopy revealed two kinetically distinct phases in the pore formation process, both of which were critically dependent on cardiolipin levels. The initially fast adsorption of Bax on the mitochondrial membrane surface is followed by a slower formation of pores and Bax-lipid clusters on the membrane surface. Our findings provide a robust molecular understanding of mitochondrial membrane perforation by cell-killing Bax protein and illuminate the initial phases of programmed cellular death.

DOI: https://doi.org/10.1126/sciadv.adg7940

Front Cell Infect Microbiol. 2023 ;13 1135203

Role of UPRmt and mitochondrial dynamics in host immunity: it takes two to tango.

Manmohan Kumar, Shagun Sharma, Shibnath Mazumder.

The immune system of a host contains a group of heterogeneous cells with the prime aim of restraining pathogenic infection and maintaining homeostasis. Recent reports have proved that the various subtypes of immune cells exploit distinct metabolic programs for their functioning. Mitochondria are central signaling organelles regulating a range of cellular activities including metabolic reprogramming and immune homeostasis which eventually decree the immunological fate of the host under pathogenic stress. Emerging evidence suggests that following bacterial infection, innate immune cells undergo profound metabolic switching to restrain and countervail the bacterial pathogens, promote inflammation and restore tissue homeostasis. On the other hand, bacterial pathogens affect mitochondrial structure and functions to evade host immunity and influence their intracellular survival. Mitochondria employ several mechanisms to overcome bacterial stress of which mitochondrial UPR (UPRmt) and mitochondrial dynamics are critical. This review discusses the latest advances in our understanding of the immune functions of mitochondria against bacterial infection, particularly the mechanisms of mitochondrial UPRmt and mitochondrial dynamics and their involvement in host immunity.

Keywords: ATFS-1; DRP1; MFN1; MFN2; UPRmt; bacterial infection; mitochondrial dynamics

DOI: https://doi.org/10.3389/fcimb.2023.1135203

Cell Mol Life Sci. 2023 Jun 02. 80(6): 173

Mitochondria as central hubs in synaptic modulation.

Filipe V Duarte, Daniele Ciampi, Carlos B Duarte.

Mitochondria are present in the pre- and post-synaptic regions, providing the energy required for the activity of these very specialized neuronal compartments. Biogenesis of synaptic mitochondria takes place in the cell body, and these organelles are then transported to the synapse by motor proteins that carry their cargo along microtubule tracks. The transport of mitochondria along neurites is a highly regulated process, being modulated by the pattern of neuronal activity and by extracellular cues that interact with surface receptors. These signals act by controlling the distribution of mitochondria and by regulating their activity. Therefore, mitochondria activity at the synapse allows the integration of different signals and the organelles are important players in the response to synaptic stimulation. Herein we review the available evidence regarding the regulation of mitochondrial dynamics by neuronal activity and by neuromodulators, and how these changes in the activity of mitochondria affect synaptic communication.

Keywords: Cannabinoid receptors; Intracellular signalling; Intracellular trafficking; Mitochondria; Neurotrophins; Synaptic regulation

DOI: https://doi.org/10.1007/s00018-023-04814-8