Cells can remain functional despite damage to mitochondria

Date:
August 31, 2020
Source:
Max-Planck-Gesellschaft
Summary:
Mitochondria are the power plants of our cells and play an important
role in providing energy for normal function of the tissues in
our body.

Thanks to a metabolic adjustment, cells can remain functional
despite damage to the mitochondria.



FULL STORY ========================================================================== Mitochondria are the power plants of our cells and play an important role
in providing energy for normal function of the tissues in our body. Nerve
cells are particularly dependent on mitochondria for their activity
and decreased mitochondrial function is seen in both inherited and more
common age-associated forms of degenerative diseases. A long-standing
view has been that neurons, in contrast to other cell types, cannot
adjust their metabolism to compensate for mitochondrial dysfunction,
and therefore irreversibly degenerate. In a new study, researchers from
the Max Planck Institute for Biology of Aging in Cologne, Germany, and
the Karolinska Institute in Stockholm, Sweden, challenge this dogma by
showing that neurons have the potential to counteract degeneration and
promote survival by adapting their metabolism.


==========================================================================
In our increasingly ageing society, neurodegenerative diseases are posing
a significant burden. A growing body of evidence has linked mitochondrial dysfunction to some of the most devastating forms of neurodegeneration,
such as Parkinson's disease, different ataxias and several peripheral neuropathies.

However, despite the urge to find strategies to prevent or arrest neurodegeneration, our understanding of the precise events underlying
neuronal death caused by mitochondrial dysfunction is very limited. "We generally tend to consider neurons as terminally differentiated cells
with very limited or no capacity to adapt their energy metabolism
to challenging conditions," says Elisa Motori, a lead author of this
study. "For some neurological diseases there is ample evidence that mitochondrial dysfunction can be tolerated for lengthy periods of time. We therefore asked the question whether degenerating neurons may activate a program of metabolic resilience." The researchers devised an innovative approach to purify degenerating neurons from the mouse brain and analyze
the global protein content (proteome) of these neurons. "Unexpectedly,
the proteomic data showed the existence of a precisely coordinated, neuron-specific metabolic program that becomes activated in response to mitochondrial dysfunction," continues Motori.

Metabolic rewiring In particular, the authors identified a form
of metabolic rewiring (Krebs cycle anaplerosis) that makes neurons
resistant to an otherwise very rapidly progressing degeneration. This
type of metabolic adaptation was previously only thought to occur in
peripheral tissues or supporting cells (glia cells) in the brain. "The
finding that neurons can induce anaplerosis was not only intriguing,
but we could further demonstrate that it had a protective role.

When we blocked anaplerosis neurons died at a much faster pace and the
disease became more severe." explains Elisa Motori.

The identification of certain forms of metabolic rewiring in dysfunctional neurons provide new mechanistic insights into the processes leading to neurodegeneration. Based on these new findings, the authors hope that it
may be possible to develop therapeutic approaches to prolong neuronal
survival and improve function in patients with mitochondrial diseases
and other types of neurodegeneration.


========================================================================== Story Source: Materials provided by Max-Planck-Gesellschaft. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. E. Motori, I. Atanassov, S. M. V. Kochan, K. Folz-Donahue,
V. Sakthivelu,
P. Giavalisco, N. Toni, J. Puyal, N.-G. Larsson. Neuronal
metabolic rewiring promotes resilience to neurodegeneration caused
by mitochondrial dysfunction. Science Advances, 2020; 6 (35):
eaba8271 DOI: 10.1126/ sciadv.aba8271 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200831094713.htm

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