(cross-posted from Imperial Mitochondriacs)
Mitochondria are components of
the cell which are involved in generating “energy currency”
molecules called ATP across much of complex life. Since many
mitochondria exist within single cells (often hundreds or thousands),
it is possible for the characteristics of individual mitochondria to
vary within cells, and within tissues. This variation of
mitochondrial characteristics can affect biological function and
human health.
Since mitochondria possess
their own, small, circular, DNA molecules (mtDNA), we can split
mitochondrial characteristics into two categories: genetic and
non-genetic. In our review, we discuss a number of aspects in which
mitochondria vary, from both genetic and non-genetic perspectives.
In terms of mitochondrial
genetics, the amount of mtDNA per cell is variable. When a cell
divides, its daughters receive a share of its parents mtDNA, but the
split isn’t precisely 50/50, so cell division can cause variability
in the number of mtDNAs per cell. As mtDNAs are replicated and
degraded over time, errors in the copying process may give rise to
mtDNA mutations, which may spread throughout a cell. Factors such as:
the total amount, the rate of degradation/replication, the mean
fraction of mutants, and the extent of fragmentation in the
mitochondrial network, can all influence how variable the fraction of
mutated mtDNAs becomes through time (see
here for a preview of some upcoming work on this topic). The
total amount, and mutated fraction of mtDNAs, are implicated in
diseases such as neurodegeneration, as well as the ageing process.
Apart from genetic variations,
there are many non-genetic features of mitochondria which also vary
within and between cells. Changes in mtDNA sequence
can change the amino-acid sequence of the proteins encoded by mtDNA,
causing structural changes in the molecular machines which generate
ATP. The shape of the membranes of mitochondria are also highly
variable, and respond to mitochondrial activity through quantities
such as pH, where mitochondrial activity itself may depend on mtDNA
sequence. The previous two examples (mitochondrial protein and
membrane structure) demonstrate how the genetic state of mitochondria
may influence their non-genetic characteristics. Mitochondrial
non-genetic characteristics may also influence the genetic state: for
instance, mitochondrial membrane potential can influence the
probability of a mitochondria being degraded, along with its mtDNA.
The
inter-dependence of genetic and non-genetic characteristics
demonstrate the complex feedback loops linking these two aspects of
mitochondrial physiology. We suggest here that, since changes in
mitochondrial genetics occur more slowly than most physical aspects
of mitochondrial physiology, understanding mitochondrial genetics may
be especially important in explaining phenomena such as ageing, which
appears
to be closely related to mitochondrial heterogeneity. You
can freely access our work, which has recently been published in
Frontiers in Genetics, as “Mitochondrial Heterogeneity”
https://www.frontiersin.org/articles/10.3389/fgene.2018.00718/full
Juvid, Iain and Nick.
