Linking Mitochondria to Neurological Disease



I’m a novice at immunology. I guess I am confused because the granules are generated over time inside the cell. At some point one would think the granule would be presented to the outside. There is also the problem that the granules are indestructible, so if the immune system gets activated it may not be able to complete its mission as it were.


Are the motor proteins you discussed (milton, miro KHC) unique to mitochondrial motility, or are they involved in other organelle transport?


Good question! there are definitely PINK1/Parkin independent forms of mitophagy, but the real regulation of mitophagy in vivo is not so clear. Indeed, mitochondrial geneticists are always wishing that the dysfunctional mitochondria within these inherited diseases would be cleared. But they aren’t… So I think the jury is still out on the specific factors that initate mitophagy in vivo, and whether distinct molecular players respond to distinct damages.


How do I get to see the live chat?


what is the level of change of calcium uptake by mitochondria in normal vs pathological condition, e.g. AD. In cardiac myocyte, it has been suggested that mitochondria does not act as a significant dynamic buffer. How much do we know about this in neuron?


milton and Miro are unique to mito, but KHC also moves other cargoes.


Is there a way to use CRISPR to alter mitrochondrial genes in order to restore their functionality?


You are right. Inside the cell they won’t do anything in terms of immunology. Only when released outside to active cell surface receptors would there be the trigger. The idea is to recruit macrophages, etc to the site so they may clean up the mess. But this can backfire if too many immune cells, microglia, etc get into the zone.


Got it thanks


We can see you! Welcome. Go ahead with any questions.


Are there any specific drugs being tested that will modify mito dysfunctions after a TBI or stroke?


Question from registration:
After traumatic brain injury mitochondrial dysfunction is known to magnify the primary injury. Can this be overcome by increased mitochondrial biogenesis? If so what would be the ligand or preconditioning stimuli?


Is mtDNA able to be transferred from one cell to another? Say by exosomes or some other means of transport?


This is such a great question that I have also been wondering.

Is it easier to edit the mitochondrial genome?

Could we put nuclear genes in here that are either expressed in the mitochondria normally but are deficient or any old nuclear gene that is deficient

First stage in gene editing?


thanks!! does the membrane potential of the inner or outer membrane oscillate in neurons like in cardiac cells? if yes, frequency?


In AD I don’t recall offhand what the fold-change is, but there are papers from Gyorgy Hajnoczky’s lab (Thomas Jefferson U) where they have measured this. Peter Hollenbeck (Purdue) may also have measured this in neurons.


not that I know. but it is even unclear how mitochondria respond after TBI or stroke


Yes, recent papers over the last 3-4 years indicate that mitos (and mtDNA) travel through “nanotunnels” from cell to cell, buut the mechanism is unknown, but exosomes and ectosomes have also been invoked as a mechanism.


I thought that might be the case. Thanks. I’ll keep searching though


thanks!! is there gap-junction like connections between mitoc and other membranes?